Active control trials for epilepsy: avoiding bias in head-to-head trials.
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Anticonvulsants↗
SEARCH · PubMed Health
Results for “Randomized Controlled Trials as Topic”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
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Evidence-based practice in pediatric surgery.
BACKGROUND/PURPOSE: The current medical environment demands the provision of quality healthcare at an affordable cost. Both payors and regulators are committed to lowering cost through initiation of best practice strategies that include practice guidelines, clinical pathways, and standards of care. The only practical way to join this debate is through the use of objective, unbiased clinical data. This study was undertaken to review the current state of the pediatric surgery literature and its value in determining best clinical practice. METHODS: The National Library of Medicine Medline database was accessed using the Ovid Internet client software. All references, abstracts, and keyword indexes from the core pediatric surgery literature, the Journal of Pediatric Surgery, the European Journal of Pediatric Surgery, Pediatric Surgery International, Zeitschrift fur Kinderchirurgie, and Seminars in Pediatric Surgery were downloaded and reviewed. Search criteria were defined to identify prospective, randomized, controlled studies. References were then categorized as case reports; retrospective case series; prospective case series; randomized, controlled studies; laboratory studies; review articles; or miscellaneous studies. RESULTS: As of March 1, 1998, there are 9,373 references, excluding citations of letters or comments, contained in the core pediatric surgery literature, as provided through Medline. Of these, 485 were identified as studies for review, possible prospective case series or prospective, randomized, controlled studies. After review, 34 studies (0.3%) were classified as prospective, randomized, controlled studies, whereas 139 (1.48%) were classified as prospective studies. There were 3,241 (34.6%) case reports, 5,619 (59.9%) retrospective case series, 1,109 (11.8%) laboratory studies, 195 (2.1%) review articles, and 36 (0.3%) miscellaneous studies that did not fit into other categories. When analyzed by decade of publication, prospective studies and prospective, randomized, controlled studies (n = 173) numbered 103 in the 1990s, 63 in the 1980s, and seven in the 1970s. CONCLUSIONS: There is a paucity of scientifically rigorous data on which to base clinical practice in pediatric surgery. The increasing numbers of prospective, case-controlled studies or the more sound prospective, randomized, controlled trials in the 1990s suggests that pediatric surgeons are aware of the need to generate unbiased data to support current clinical practice and the development of practice guidelines. Limitations exist in conducting prospective, randomized, controlled trials because of the rare nature of many pediatric surgical conditions and the lack of clinical "equipoise" over available treatment options. The authors encourage the use of multiinstitutional trials and the prospective, randomized, controlled study methodology to develop data that can be used to guide clinical practice in our evolving healthcare environment.
Evidence-Based Medicine↗
[Thrombolytics and neuroprotective agents in the treatment of the patient with an acute cerebrovascular ischemic accident].
INTRODUCTION: Cerebrovascular disease occupies second place amongst the causes of mortality in the world. Rapidly after onset of an acute ischemic cerebrovascular accident (CVA) there is irreversible formation of an area affected by the ischemic process (necrotic centre) surrounded by a zone in which reduction of blood flow is less marked. Although the neurons of this region, known as the 'ischemic penumbra', are in a state of 'electrical silence', they may recover if effective treatment is started in time. DEVELOPMENT: Treatment of the patient with an acute ischemic CVA should be concentrated in two areas: restoration of blood flow and neuroprotection. In spite of better understanding of the biochemical, genetic and molecular processes which occur during the process of cerebral ischemia, the development of neuroprotector strategies has been largely fruitless. However, restoration of cerebral blood flow is currently possible in a certain group of patients. The fibrinolytic system is formed by an inactive proenzyme, plasminogen, which may be converted to the active form, plasmin, in the presence of specific activators such as tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). CONCLUSIONS: The effect of thrombolytic treatment is due to dissolution of the fibrin present in the occluding thrombus, with subsequent restoration of the blood flow to the ischemic area. Nevertheless the use of thrombolytic agents has dramatically changed the clinical management of patients with acute ischemic cerebrovascular incidents. Their use involves a significant risk of intracerebral bleeding, which together with the narrow therapeutic window, has made this one of the most controversial fields of current neurology.
Acute Disease↗
High dose therapy and autologous hemopoietic stem cell transplantation in rheumatoid arthritis--the feasibility of phase III trials.
If a niche is to be established for autografting in the treatment of severe rheumatoid arthritis (RA), investigators should have the common goal of providing higher levels of evidence. Autografting in RA can be envisaged only for severe RA that has resisted all safer available treatments, and given the relatively large numbers necessary for statistical power in randomized studies, investigators will need to work together. This article summarizes the current literature and discusses practical issues relating to future trials.
Arthritis, Rheumatoid↗
NCX-701. NicOx.
NicOx is developing NCX-701, a nitric oxide-releasing derivative of paracetamol (acetaminophen), for the potential treatment of inflammation and pain. The compound is currently undergoing phase III clinical trials.
Acetaminophen↗
Informed consent: practices and views of investigators in a multinational clinical trial.
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Clinical Trials, Phase III as Topic↗
High-dose chemotherapy and hematopoietic stem cell transplantation for relapsed or refractory diffuse large-cell non-Hodgkin's lymphoma.
The use of high-dose chemotherapy and transplantation for chemotherapy sensitive relapsed diffuse large-cell non-Hodgkin's lymphoma is now the gold standard for patients who are candidates for such therapy. Recent data also demonstrates the relative effectiveness of this approach for patients who are induction failures but are continuing to respond to conventional therapy at the time of transplantation. Newer approaches such as the use of novel agents to modify the transplant regimen, newer cytokines, or alternative sources of hematopoietic stem cells need to be tested in order to improve the outcome in patients with chemotherapy resistant disease.
Antineoplastic Combined Chemotherapy Protocols↗
An overview of the safety of isepamicin in adults.
The safety profile of isepamicin has been assessed from a series of phase II and III clinical trials. A total of 1243 patients were randomised to treatment with isepamicin, mainly administered once daily at a dose of 15 mg/kg or 8 mg/kg depending on the severity of infection. A small proportion of patients were randomised to isepamicin at a dosage of either 7.5 mg/kg twice daily or 4 mg/kg twice daily. In the majority of studies, isepamicin was compared with a standard twice-daily dosing regimen of 7.5 mg/kg amikacin = (n - 552). The clinical studies included patients with a variety of bacterial infections, including lower respiratory tract, urinary tract, intra-abdominal and skin and skin structure infections. The study aminoglycosides were co-administered with other antimicrobial agents in line with normal clinical practice depending on the site, nature and severity of infection. Most patients received isepamicin or amikacin as a 30-minute intravenous infusion and a small proportion of patients with less severe infections received intramuscular injections. The mean duration of treatment was nine days for both the isepamicin and amikacin treatment groups, and was similar for patients with both severe and less severe infections. Overall, the proportion of patients reporting any adverse event was comparable between the isepamicin (13%) and amikacin (11%) groups. No individual adverse event was reported in more than 2% of patients, the most commonly reported events being phlebitis, rash, headache and renal compromise. The frequency of adverse events was not influenced by treatment duration, age or gender. Treatment-related adverse events which were considered severe or life-threatening were reported in 1.8% of patients receiving isepamicin and 2.0% of patients receiving amikacin. Two per cent of patients in each treatment group discontinued the study because of adverse events and 2% of patients in each treatment group died during treating. Four per cent of patients in each treatment group died within 30 days after the end of treatment. Changes in laboratory tests were similar in both treatment groups; few changes were considered by the investigators to be treatment-related. Increases in serum creatinine indicative of possible renal compromise occurred in 4.6% of isepamicin and 5.1% of amikacin patients. The occurrence of ototoxicity as measured by standard frequency pure tone audiometry was low. In summary, isepamicin is a sell-tolerated aminoglycoside with a safety similar to that of amikacin.
Adult↗
Hidden evidence to the West: multicentre, randomised, controlled trials in sepsis and systemic inflammatory response syndrome in Japanese journals.
OBJECTIVE: To assess multicentre, randomised, controlled trials (MC-RCTs) of systemic inflammatory response syndrome (SIRS) and sepsis conducted in Japan, published in Japanese and not available to English-language medical databases. DESIGN: Methodological review. SUBJECTS: All Japanese RCTs relevant to SIRS and sepsis. INTERVENTION: Identification of manuscripts using a Japanese electronic library. Critical analysis of methodology and reporting quality using a modified Methodological Quality Assessment Score and the CONSORT group check list. MEASUREMENTS AND RESULTS: Three MC-RCTs were identified. In the first, 147 patients with septic shock were randomised to methylprednisolone (1000 mg i.v.) or placebo. In the second, 221 patients were randomised to 0.20 mg/kg per h or 0.004 mg/kg per h of sivelestat for acute lung injury with SIRS. In the third, 504 patients were randomised to immunoglobulin (5 g for 3 days) or to a control group. The average methodological quality score was higher than that of equivalent Western trials. The reporting quality (CONSORT checklist) was comparable to Western studies published during the same period. CONCLUSIONS: Despite sound methodology and quality, the information obtained from relatively large Japanese critical care trials is not widely available to English-speaking investigators and therefore might be ignored in meta-analyses.
Anti-Inflammatory Agents↗
Randomized consent designs for clinical trials: an update.
Randomized consent designs were introduced to make it easier for physicians to enter patients in randomized clinical trials. Physician reluctance to participate in randomized clinical trials is often a reflection that the physician-patient relationship could be compromised if the physician makes known to the patient his/her inability to select a preferred therapy. Clinical trials having a no-treatment control or placebo amplify this concern. This paper reviews the main ideas of randomized consent designs (single and double) and the statistical model underlying the analysis, and presents some recent experiences.
Informed Consent↗
From the parallel group design to the crossover design, and from the group approach to the individual approach.
The consequences of heterogeneity in response to antihypertensive drugs for the clinical development programs of new antihypertensive drugs and for the care of the individual hypertensive patient have not previously been sufficiently recognized. They play a role in the inappropriate choice of too-high daily doses of some antihypertensive drugs at the end of extensive international development programs. They are also implicated in the insufficient control of blood pressure observed in the long-term multicenter trials in hypertension, where some patients have been treated for several years with drugs that were not the most appropriate for their disease and which did not adequately control their blood pressure. In addition to the parallel group studies, the use of double-blind two-period or multiple period crossover designs can provide valid data for the dose-finding of new antihypertensive drugs and their comparative evaluation. At the end of the trial, these designs also offer each patient the opportunity to be treated with the right dose of the drug most appropriate for his or her disease.
Antihypertensive Agents↗
A checklist to evaluate a report of a nonpharmacological trial (CLEAR NPT) was developed using consensus.
BACKGROUND AND OBJECTIVE: To develop a checklist of items measuring the quality of reports of randomized clinical trials (RCTs) assessing nonpharmacological treatments (NPTs). STUDY DESIGN AND SETTING: The Delphi consensus method was used to select and reduce the number of items in the checklist. A total of 154 individuals were invited to participate: epidemiologists and statisticians involved in the field of methodology of RCTs (n = 55), members of the Cochrane Collaboration (n = 41), and clinicians involved in planning NPT clinical trials (n = 58). Participants ranked on a 10-point Likert scale whether an item should be included in the checklist. RESULTS: Fifty-five experts (36%) participated in the survey. They were experienced in systematic reviews (68% were involved in the Cochrane Collaboration) and in planning RCTs (76%). Three rounds of the Delphi method were conducted to achieve consensus. The final checklist contains 10 items and 5 subitems, with items related to the standardization of the intervention, care provider influence, and additional measures to minimize the potential bias from lack of blinding of participants, care providers, and outcome assessors. CONCLUSIONS: This tool can be used to critically appraise the medical literature, design NPT studies, and assess the quality of trial reports included in systematic reviews.
Consensus↗
Adjuvant therapy of melanoma: what's new?
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Chemotherapy, Adjuvant↗
Rationale and methodology of the multicenter pediatric cerebrospinal fluid shunt design trial. Pediatric Hydrocephalus Treatment Evaluation Group.
Cerebrospinal fluid shunt failure remains a common and at times overwhelming problem in pediatric patients with hydrocephalus. Two new shunt valve designs, the Orbis-Sigma (Cordis Corporation, Miami, Florida) and the Delta valve (PS Medical, Goletta, California), have flow/pressure characteristics dramatically different from those of standard differential pressure valves which have been used for over three decades. Both new designs reduce the siphoning effect in the upright position, and have been reported to reduce shunt failure rates in uncontrolled series, allegedly due to reduction in shunt overdrainage. Most mechanical shunt failure in the first 2 years after implantation is due to proximal shunt obstruction, overdrainage, and loculated ventricles. By reducing the incidence of slit ventricles associated with standard valves, both new designs could be envisioned as reducing the early mechanical complications. The improved results with both new valves could, however, also be to a large extent due to other confounding effects of shunt surgery, including patient selection, surgical technique, and specific configuration of the components of the shunt other than the valve. There are also theoretical reasons why these valve designs might be worse than their predecessors, including the narrow orifice and high resistance of the Orbis-Sigma, and the flexible membrane of the siphon control portion of the Delta valve, which may increase the ventricular pressure in the upright position or become blocked by encasing scar tissue. For this reason a randomized trial is required to determine efficacy, and a standard differential pressure valve is required as the control design. A significant reduction in early shunt failure would dramatically improve the morbidity and mortality of pediatric hydrocephalic patients, as well as providing substantial savings to the health care system. Failure to determine any difference would focus attention on other issues surrounding shunt surgery, such as patient characteristics or surgical technique.
Cerebrospinal Fluid Shunts↗
Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.
The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C < 100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
Aged↗
Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.
The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
Aged↗
Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.
The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
Aged↗
Clinical trials with implications regarding heart failure therapy.
Paradigms for the treatment of heart failure have changed substantially over the past several decades. It has been the performance of relatively large, carefully controlled and often mortality endpoint trials that has given us great insight into therapies that are advantageous, disadvantageous, or neutral with respect to outcomes in patients with heart failure. No longer is the care of a patient with ventricular dysfunction and heart failure solely rooted in the prescription of a diuretic and digoxin. Indeed, we have seen a rather radical evolution from this prescription practice to approaches that were thought to be contraindicated at one time, such as beta blocker and vasodilator therapy. Indeed, treatment paradigms today are shifting rapidly toward more complete attenuation of adrenergic processes known to be detrimental in this setting. It is important to review the recent clinical trials that have given us further insight into managing heart failure. Twenty trials published since 1995 have been selected because of the important insight they give us regarding the wide spectrum of therapeutic options available for individuals with heart failure.
Double-Blind Method↗