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Results for “Clinical Trials, Phase II as Topic”

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At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Missing data in quality of life research in Eastern Cooperative Oncology Group (ECOG) clinical trials: problems and solutions.

Incorporation of quality of life (QOL) investigation into Eastern Cooperative Oncology Group (ECOG) multi-centre clinical trials has led to innovative strategies for protocol design and high quality data collection. A scientific advisory committee reviews protocol design components, measurement selection, timing of assessments and compliance issues. Extensive educational programmes provide information about the scientific and clinical relevance of QOL protocols, as well as practical strategies for data collection and management. Compliance with QOL data collection standards is prospectively monitored and evaluated. Preliminary results from eight ECOG-run protocols found overall compliance to be approximately 85 per cent (94 per cent at baseline and 73 per cent during treatment). Selected patient and institutional factors were evaluated for their association with compliance.

Adult↗
PubMedDate not supplied

Quality of life as an endpoint in EORTC clinical trials. European Organization for Research and Treatment for Cancer.

For more than 30 years the European Organization for Research and Treatment for Cancer (EORTC) has conducted, co-ordinated, and stimulated research on the experimental and clinical bases of treatment of cancer and related problems. For more than a decade the EORTC has included quality of life as an outcome measure in some of its trials. The number of clinical studies that include QOL as an evaluation endpoint has increased rapidly in the last few years, and is still increasing steadily. This necessitated a careful and critical evaluation of procedures and results so far in order to generate appropriate guidelines and procedures for incorporating QOL issues in all stages of the clinical trial process, including protocol writing, data collection, data analysis, and reporting of results. This paper provides an overview of the types and the design of studies, data management of quality of life assessment, compliance, missing data and lessons learned during the past years with respect to QOL assessments in the EORTC studies.

Adult↗
PubMed2001

Issues in the assessment of the safety and efficacy of tenecteplase (TNK-tPA).

While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety of alteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 lb) without an increased risk of ICH or death. Furthermore, the results of TNK-tPA clinical trials showed that even at the highest weight-optimized dosage of 50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. In elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.

Body Weight↗
PubMed2007

A 25-year review of sequential methodology in clinical studies.

This paper explores the theoretical developments and subsequent uptake of sequential methodology in clinical studies in the 25 years since Statistics in Medicine was launched. The review examines the contributions which have been made to all four phases into which clinical trials are traditionally classified and highlights major statistical advancements, together with assessing application of the techniques. The vast majority of work has been in the setting of phase III clinical trials and so emphasis will be placed here. Finally, comments are given indicating how the subject area may develop in the future.

Clinical Trials as Topic↗
PubMedDate not supplied

Use of photodynamic therapy for the management of pleural malignancies.

Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention being investigated for oncologic therapy. Surfaces such as the pleura or the peritoneum are frequently involved with primary or metastatic cancer, and the chance for cure in such situations is low due to the inability to eradicate all the disease. A series of investigations have been performed at the National Cancer Institute since 1985 studying the possible use of PDT for large cavity treatment. This report details evolution of the methodology, toxicity, and overall feasibility of the delivery of intrapleural PDT to patients after debulking of primary and malignant chest neoplasms, with an emphasis on malignant pleural mesothelioma. These investigations have culminated in an ongoing Phase III trial to define the efficacy of intrapleural PDT.

Animals↗
PubMed1996

A proposed design for conducting target animal safety studies for developing new veterinary pharmaceuticals.

Target animal safety studies are required for the regulatory approval of any new veterinary pharmaceutical registered almost anywhere in the world. Both the United States and Europe have extensive guidelines for conducting these studies. Due to new veterinary drug labeling requirements in the United States, changes in the overall design of target animal safety studies will be required for the United States. The guideline changes proposed in this paper are more evolutionary than revolutionary. While many new ideas are suggested, a number of existing practices that seem to work well were retained. Several new abbreviated drug development pathways are also proposed, an idea missing from current guidelines. This proposal, and others like it, should serve as a basis for representatives from the U.S. Food and Drug Administration, the European Commission on Veterinary Medical Products, the veterinary pharmaceutical industry, and practicing veterinarians to develop internationally harmonized target animal safety study guidelines that are clear in their intent, scientifically sound, and practical.

Animal Welfare↗
PubMed2005

Biostatistical methods for demonstrating efficacy in the regulatory setting. An epistemological approach to adaptive designs.

Adaptive designs are one of the most promising developments in statistics with applications to clinical trials. Obviously the knowledge at the beginning of a clinical trial will always be limited. In consequence it may be considered necessary that the knowledge from accumulating information should be used to optimize the design of the trial. This paper discusses conditions under which this may be possible in phase III clinical trials where the principle aim is confirmation of hypotheses that have been developed in earlier stages of drug development.

Biometry↗
PubMed2005

[Clinical trials. An overview].

Since the mid-1950s, the basis for evaluating medical therapies has shifted from transferred knowledge, subjective impression and personal experience towards clinical trials, first, in reaction to side effect tragedies, in drug licensing, then to a growing extent in other parts of medicine such as the assessment of medical devices or surgical procedures. Clinical trials are prospective studies of the efficacy and safety of therapies by repeated application. For this purpose, therapies are usually compared to controls, based on statistical reasoning. Initial comparability of study groups is best guaranteed by randomisation while equality of observation and of concomitant treatment is best guaranteed by blinding. Clinical trials do not result in clear-cut yes/no answers, but reduce the range of reasonable interpretations regarding efficacy and safety of a therapy. Thus, they allow decisions to be made on solid objective grounds. In this way, clinical trials have contributed substantially to medical progress over the last 50 years and are indispensable for today's medical research.

Clinical Trials as Topic↗
PubMed2002

Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications.

Ferucarbotran (Resovist) is the second clinically approved superparamagnetic iron oxide developed for contrast-enhanced MRI of the liver. The purpose of this review is to provide an overview on the properties, clinical development, and application of ferucarbotran. Safety data obtained during clinical phases I-III revealed a total of 162 adverse events within 1053 patients, of which 75 were classified as possibly, probably, or definitely drug related. The majority of events occurred within the first 3 h (73 of 75) and was of mild intensity. The agent significantly improves the detection of hypovascular focal liver lesions with a comparable sensitivity in lesion detection to CTAP but without a relevant loss in specificity. Furthermore, ferucarbotran leads to a significant improvement of the sensitivity for lesion classification and characterization of the most frequent liver lesions. Contrast-enhanced MRA is not feasible and the angiographic effect is not sufficient to allow for postprocessing of data into maximum intensity projections. Intraindividual studies at low-field (0.2 T) and high-field (1.5 T) showed similar rates for lesion detection. The time window for contrast-enhanced MRI of the liver is at least 1 day up to 4 days. The compound can be regarded as safe and well tolerated. Even bolus injections caused no cardiovascular side effects, lumbar back pain, or clinically relevant laboratory changes. The examination time can be kept short with T1- and T2-weighted pre-contrast sequences, dynamic MRI over 10 min, and finally accumulation phase T2-weighted MRI. Patients who may benefit in particular are surgical candidates for resection, transplantation, or interventional therapies, and patients with liver cirrhosis and/or suspected hepatocellular carcinoma to either exclude malignancy or to define the extent of disease, the location of lesions, and the type of newly detected lesions.

Clinical Trials, Phase I as Topic↗
PubMed2003

[Pharmacological therapy for age-related macular degeneration. Current developments and perspectives].

Current therapeutic options for age-related macular degeneration are very limited and are, at best, only capable of slowing visual loss. Because of this an intensive search for prophylactic agents capable of inhibiting the progression of this disease from early into late forms, as well as for new therapeutic approaches has been undertaken. While neuroprotective substances are hoped to prevent cellular death in this disease process, multiple substances capable of inhibiting neovascularization, such as VEGF inhibitors, are in clinical trials. Inhibitors of matrix-metalloproteinases (MMP) and chemotherapeutic agents are also being clinically tested as novel therapies for AMD. Other targets include the inhibition of toxic compound formation in lipofuscin granules such as AZ-E. What follows is an overview of different substances and their stages of development in clinical trials.

Adrenal Cortex Hormones↗
PubMed2002

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma.

The clinical development and US Food and Drug Administration approval in 1997 of the monoclonal anti-CD20 antibody rituximab have been major treatment advances for patients with B-cell non-Hodgkin's lymphoma (NHL). Rituximab produces responses in approximately 50% of cases of relapsed, low grade NHL. Most of these responses are partial remissions; cure remains elusive. One way to enhance the effectiveness of monoclonal antibodies is to chelate radionuclides such as yttrium-90 ((90)Y) to the antibody. ( 90)Y is a high-energy, beta-emitting radioisotope that delivers most of its radiation over a path length of 2 to 5 mm. Therefore, the antibody delivers, or targets, the radiation only to CD20+ cells, sparing normal cells from the radiation. Ibritumomab is the murine anti-CD20 antibody that was engineered to develop the human chimeric antibody rituximab. Tiuxetan is a linker/chelator that is attached to the antibody to form ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA). Zevalin can be reacted with (111)indium ((111)In) for imaging and (90)Y for therapy. Phase I studies of Zevalin have determined that patients with a baseline platelet count greater than 150,000 10(6)/L receive 0.4 mCi/kg. Patients with a platelet count of 100 to 149,000 10(6)/L should receive 0.3 mCi/kg. Zevalin has a higher overall response rate (ORR) than its cold antibody counterpart rituximab, as demonstrated in two separate clinical trials. The first trial (IDEC 106-04) randomized 143 rituximab-naïve patients with relapsed NHL to receive rituximab or Zevalin. The ORR for Zevalin was 80% compared with 56% for rituximab (P = 0.002). The second trial (IDEC 106-06) tested the efficacy of Zevalin in patients who were rituxan-refractory; the ORR was 74%. The main toxicity of Zevalin was reversible myelosuppression. These studies indicate that radiolabeled anti-CD20 antibodies can produce a higher ORR than rituximab. Single-dose Zevalin is another treatment alternative for patients with relapsed low grade NHL. It is well-tolerated even by older adults. The exact role of Zevalin in the therapy of NHL is undetermined. New studies are underway to explore whether patients can safely receive a second dose of Zevalin and to combine Zevalin with high-dose chemotherapy and stem cell rescue. The outcome of these studies will be helpful in deciding how best to integrate this new modality into the treatment paradigm of NHL.

Antibodies, Monoclonal↗
PubMed1996

Clinical profile of the novel sulphonylurea glimepiride.

Glimepiride is a new generation sulphonylurea being prudently characterized in more than 2000 NIDDM patients. It has a short onset of action and a long duration of action. The same pharmacodynamic effect as with traditional sulphonylureas is achieved with secretion of less insulin, suggesting a possible extrapancreatic action. Glimepiride is given once daily in doses from 1-8 mg/day. 100% absolute bioavailability and the absence of a food interaction guarantee highly reproducible pharmacokinetics. Glimepiride is a remarkably safe drug especially in NIDDM patients at high risk e.g. the renally impaired, elderly or physically very active person. Hypoglycemia is less frequent in the first weeks of treatment than with glibenclamide. Ongoing studies are investigating the possible beneficial clinical effect of its different binding behavior to the potassium channel, especially in the heart.

Blood Glucose↗
PubMed2006

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report.

The complexity of chronic graft-versus-host disease (GVHD) and the lack of established research methods have made it difficult to design, conduct, and analyze clinical trials involving subjects with this disease, even when promising treatment options are available. This consensus document was developed to offer an approach for overcoming these obstacles. Clinical trials in chronic GVHD should adhere to principles of good trial design and practice. Inclusion and exclusion criteria should allow as many subjects to participate as possible without compromising the interpretation of results. Pre-enrollment assessment of chronic GVHD characteristics should be standardized. The protocol should provide clear guidance about administration of study medication and other interventions. Methods of assessing response should be defined and validated in advance. Efficacy endpoints should be selected to reflect clinical benefit. Expert biostatistical support is needed to ensure the validity and reliability of trial results. The use of consistent standards in clinical trial designs to evaluate agents that have activity in pathogenic pathways could facilitate advances in the treatment of chronic GVHD.

Adrenal Cortex Hormones↗