Stat bite: Treatment trials in the PDQ clinical trials database, by phase.
Explore the source record for details and available documents.
Antineoplastic Agents↗
SEARCH · Search PubMed
Results for “Clinical Trials, Phase I as Topic”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Clinical trial design in metastatic breast cancer: a commentary.
Trial designs traditionally used in the development of new anti-cancer agents are usually categorized as phase I, phase II, phase III and phase IV. Such trials are often performed in patients with metastatic cancer. Phase I trials are conducted in small numbers of patients to determine a drug's maximally tolerated dose (MTD) and toxicity profile. In phase II studies, the anti-tumor activity of the new agent is tested in different tumor types. If a drug is found to be promising in phase II studies, it is then compared to standard therapy through a randomized trial design in phase III studies. In phase IV studies, the efficacy and safety profile of the drug are evaluated in a standard clinical setting. In the field of oncology, studies have been conducted in which agents already approved by the regulatory agency are combined with other anti-cancer drugs and evaluated for anti-tumor efficacy. These have also been termed phase II studies.
Antineoplastic Agents↗
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↗
[Drug clinics. Clinical drug trials: the importance and role of the general practitioner].
Clinical trials are an essential step in the development of a drug. They must be conducted according to strict rules called "Good Clinical Practice" or GCP. GCP requirements aim to guarantee a perfect methodology in the planning, realization and interpretation of clinical trials. The latter can be divided in four phases: phase 1 aiming to demonstrate the safety and to investigate the pharmacokinetics/metabolism of the drug in healthy volunteers; phase 2 aiming to study the intrinsic activity (generally versus a placebo) and safety of the compound in a rather small number of (hospitalized) patients; phase 3 aiming to confirm the comparative efficacy (versus a placebo or a reference drug) and safety of the pharmacological agent in a quite large number of (ambulatory) patients; and phase 4 carried out after commercialization, to verify the clinical utility of the drug in conditions of daily practice. Because he/she occupies a crucial position in the recruitment and follow-up of outpatients, the general practitioner should play a more active role in clinical trials, provided that he/she could work in collaboration with academic centers specialized in clinical pharmacology which can help to perform studies in accordance with GCP requirements.
Academic Medical Centers↗
Therapeutic vaccine trails in Thailand.
An effective therapeutic HIV vaccine will not only benefit the HIV-infected person but will also provide invaluable information on effective immune response in designing or selecting a preventive vaccine. A phase II double-blind controlled clinical trial using HIV-1 immunogen (Remune) was undertaken in Thailand in 1995 in conjunction with phase III approval in the USA. In most instances, immune response to the virus was induced. The results from this study led to the extension of further trials over the following 4 years. At present, the Thai Food and Drug Administration (FDA) is in the process of reviewing the files on all information to assess the effectiveness of this therapeutic vaccine as well as reviewing the proposal to conduct a phase III trial to further confirm previous efficacy results from the phase II trials.
AIDS Vaccines↗
[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↗
An overview of clinical trials.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Design of field trials for the evaluation of antibacterial products for therapy of bovine clinical mastitis.
In this paper, the design and statistical analysis of field trials for the evaluation of the efficacy of clinical mastitis therapeutics is covered. First, general issues underlying the design of clinical trials are reviewed. These include bias and confounding; randomization and blocking; and study objectives and choice of the corresponding hypothesis. Specific issues in the design of clinical mastitis trials are also discussed. Selection of subjects is discussed with regard to choice of experimental units, identification of reference population and study population, inclusion and exclusion criteria, and sample size calculation. Next, a section on treatment administration and evaluation of cure reviews treatment, blinding, choice of response measure, as well as compliance, withdrawal, and early termination. The statistical analysis section addresses possible statistical models, treatment of confounding, and fixed vs. random effects. In conclusion, well-conducted clinical mastitis trials represent an invaluable, albeit difficult and expensive, effort to evaluate efficacy and tolerance under usual circumstances of use.
Animals↗
How pharmacogenomics will impact the federal regulation of clinical trials and the new drug approval process.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
A phased approach to clinical testing: criteria for progressing from Phase I to Phase II to Phase III studies.
The overall intent of clinical testing is to establish, in a series of phased studies, the clinical tolerance and acceptable "safety" of the candidate vaccine, as well as the type, level and persistence of the immune response after its inoculation, to a representative target population, according to a convenient administration schedule. The final stages involve the direct or indirect demonstration of protective efficacy, if possible in the population(s) for which the vaccine is intended. In addition, consistency of production must be demonstrated. At all these stages, the amount of prior information from preclinical and other studies affects and informs the objectives and design of subsequent studies. Progression from one testing phase to the next is dependent upon attaining the pre-set objectives of each series of studies. The precise objectives to be met will be decided on a case-by-case basis. The earliest assessments in humans (Phase I) involve evaluation of short-term clinical tolerance as measured by local and general reactogenicity, and gross assessments of immunogenicity, in a small number of highly selected individuals in an idealised situation. The selection of "optimal" dose and schedule are the result of further dose-ranging investigations (Phase II), involving more volunteers, with longer, more detailed follow-up assessments. It is at this stage that the accumulated evidence on its immunogenicity profile should be sufficient to assess whether or not the vaccine is worthy of further development. The next level of investigation (Phase III) aims to measure with greater precision the vaccine protective efficacy in the intended target population(s) by comparison of infection and/or disease attack rates in vaccine and placebo recipients. In consistency studies different production lots, manufactured at commercial scale, are tested to demonstrate consistency of manufacture. Additional bridging studies to establish similarity of lots at different production scales, or studies of the duration of the immunity conferred, are conducted in parallel with the progression of the studies in the different phases mentioned above. These latter types of studies are usually carried out concurrently with Phase III studies. This progression continues into the post-marketing period (Phase IV) with surveillance of long term efficacy and observational studies of possible rare adverse events to establish "safety" with more confidence. This paper examines, in general, the aims and designs of studies in each phase as an introduction to the more specific publications that follow.
Clinical Trials as Topic↗
Clinical trial designs for targeted agents.
With an increasing number of targeted agents available for testing, clinical trials must be rationally designed based on sound knowledge of the molecular mechanisms linking target and disease, fortified by strong preclinical data demonstrating how this relationship is modified by the targeted agent. Patients and resources are precious and should be expended judiciously on clinical trials that are well planned. Although traditional trial designs and endpoints may not be adequate for developing contemporary targeted drugs, transiting directly from phase I to phase III testing should be avoided except in distinct circumstances. Increased research efforts should be spent on the prospective evaluation and validation of novel biologic endpoints and innovative clinical designs, such that promising targeted agents can be effectively developed to benefit the care of cancer patients.
Animals↗
Unconventional anticancer agents: a systematic review of clinical trials.
PURPOSE: A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. METHODS: MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. RESULTS: We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. CONCLUSION: Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.
Antineoplastic Agents↗
Tirilazad mesylate in acute ischemic stroke: A systematic review. Tirilazad International Steering Committee.
BACKGROUND AND PURPOSE: Tirilazad is a nonglucocorticoid, 21-aminosteroid that inhibits lipid peroxidation. Studies in experimental models of ischemic stroke had suggested that tirilazad had neuroprotective properties. As a result, clinical studies were undertaken to assess the safety and efficacy of tirilazad in the treatment of acute ischemic stroke. We performed a systematic review of randomized, controlled trials that assessed the safety and efficacy of tirilazad in patients with acute ischemic stroke. METHODS: Trials of tirilazad were identified from searches of the Cochrane Library and communication with the Pharmacia & Upjohn company, the manufacturer of tirilazad. Data relating to early and end-of-trial case fatality, disability (Barthel Index and Glasgow Outcome Scale), phlebitis, and corrected QT interval were extracted by treatment group from published data and company reports and analyzed by using the Cochrane Collaboration meta-analysis software REVMAN. RESULTS: Six trials (4 published, 2 unpublished) assessing tirilazad in 1757 patients with presumed acute ischemic stroke were identified; all were double-blind and placebo controlled in design. Tirilazad did not alter early case fatality (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). A just-significant increase in death and disability, assessed as either the expanded Barthel Index (OR 1.23, 95% CI 1.01 to 1.51) or Glasgow Outcome Scale (OR 1. 23, 95% CI 1.01 to 1.50) was observed. Tirilazad significantly increased the rate of infusion site phlebitis (OR 2.81, 95% CI 2.14 to 3.69). Functional outcome (expanded Barthel Index) was significantly worse in prespecified subgroups of patients: females (OR 1.46, 95% CI 1.08 to 1.98) and subjects receiving low-dose tirilazad (OR 1.31, 95% CI 1.03 to 1.67); a nonsignificant worse outcome was also seen in patients with mild to moderate stroke (OR 1. 40, 95% CI 0.99 to 1.98). CONCLUSIONS: Tirilazad mesylate increases death and disability by about one fifth when given to patients with acute ischemic stroke. Although further trials of tirilazad are now unwarranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischemic stroke.
Aged↗
New paradigm in dose-finding trials: patient-specific dosing and beyond phase I.
We propose a new paradigm for the clinical evaluation of new cancer therapies. It entails adjusting the search for the optimal dose on the basis of measurable patient characteristics that may be predictive of adverse responses to treatment, and extending this search beyond phase I and into phases II and III. We provide examples of (a) how the fine-tuning of dose may involve utilization of patient-specific attributes to obtain a personalized treatment regimen, and (b) how novel methods for phase I design can be used to update the working dose for the conduct of phase II and III cancer clinical trials. These examples should be interpreted as an enticement for the development of new methods to implement the proposed new paradigm.
Antineoplastic Agents↗
Partial breast irradiation after breast-conserving surgery.
BACKGROUND: The standard technique of postoperative radiotherapy after breast-conserving surgery is percutaneous irradiation of the entire breast to a total dose of 45-50 Gy which is usually followed by a tumor bed boost. Since the majority of local recurrences in selected patients occur close to the former tumor bed, the question arises whether a sole tumor bed irradiation might be a therapeutic alternative to total breast irradiation. METHODS: A systematic review of relevant literature concerning partial breast irradiation (PBI) up to November 2004 was undertaken. Studies of any design were included for comparison and discussion. RESULTS: Nine unique brachytherapy studies using the multi-catheter technique, one the balloon technique (MammoSite), and eight particular intraoperative radiotherapy (IORT) trials were located of which only one was a randomized trial. Only minor postoperative complications were reported. Preliminary results are similar in terms of local tumor control, disease-free and overall survival. However, the current evidence base of IORT studies is poor. CONCLUSION: Despite controversies regarding PBI after breast-conserving surgery, results of phase I-II trials suggest that sole tumor bed irradiation might be an appropriate therapeutic alternative for selected breast cancer patients. However, more experience and data from ongoing phase III trials are required to define these new methods to be an appropriate treatment option. Therefore, total breast irradiation still remains the standard irradiation modality even in the treatment of early breast cancer, and PBI should be considered investigational.
Adult↗
Statistics in clinical trials.
Statistical developments over the past several years are described in this review. Efforts in phase I studies have focused on efficient estimation of maximum tolerated dose. Issues investigated for phase II trials include incorporation of multiple endpoints and randomization. For phase III trials, methods to reduce time or use the sample size more efficiently have been investigated. However, design innovations come with costs, including possible increased risk of incorrect conclusions. Other recent challenging statistical developments in clinical trials relate to use of complementary outcomes such as quality of life and to associated biologic questions, including the emergence of the field of genomics.
Clinical Trials as Topic↗