The phases of clinical research are the steps in which scientists conduct experiments with a health intervention in an attempt to obtain sufficient evidence for a process which would be useful as a medical treatment. In the case of pharmaceutical study, the phases start with drug design and drug discovery proceed on to animal testing. If this is successful, they begin the clinical phase of development by testing for safety in a few human subjects and expand to test in many study participants to determine if the treatment is effective. Clinical trials involving new drugs are classified into four phases. Individual trials may encompass more than one phase. A common example of this is combined phase phase II/III trials. Therefore, it may be easier to think of late phase studies; the drug-development process will proceed through all four phases over many years. If the drug passes through Phases I, II, III, it will be approved by the national regulatory authority for use in the general population. Phase IV are'post-approval' studies.
Before pharmaceutical companies start clinical trials on a drug, they conduct extensive preclinical studies. These involve in vitro and animal experiments using wide-ranging doses of the study drug to obtain preliminary efficacy and pharmacokinetic information; such tests assist pharmaceutical companies to decide whether a drug candidate has scientific merit for further development as an investigational new drug. Phase 0 is a recent designation for optional exploratory trials conducted in accordance with the United States Food and Drug Administration's 2006 Guidance on Exploratory Investigational New Drug Studies. Phase 0 trials are known as human microdosing studies and are designed to speed up the development of promising drugs or imaging agents by establishing early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. Distinctive features of Phase 0 trials include the administration of single subtherapeutic doses of the study drug to a small number of subjects to gather preliminary data on the agent's pharmacokinetics.
A Phase 0 study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. Drug development companies carry out Phase 0 studies to rank drug candidates in order to decide which has the best pharmacokinetic parameters in humans to take forward into further development, they enable go/no-go decisions to be based on relevant human models instead of relying on sometimes inconsistent animal data. Phase I trials were referred to as “first-in-man studies” but the field moved to the gender-neutral language phrase "first-in-humans" in the 1990s, they are designed to test the safety, side effects, best dose, formulation method for the drug. A small group of 20–100 healthy volunteers will be recruited; these trials are conducted in a clinical trial clinic, where the subject can be observed by full-time staff. These clinical trial clinics are run by contract research organization who conduct these studies on behalf of pharmaceutical companies or other research investigators.
The subject who receives the drug is observed until several half-lives of the drug have passed. This phase is designed to assess the safety, tolerability and pharmacodynamics of a drug. Phase I trials include dose-ranging called dose escalation studies, so that the best and safest dose can be found and to discover the point at which a compound is too poisonous to administer; the tested range of doses will be a fraction of the dose that caused harm in animal testing. Phase I trials most include healthy volunteers. However, there are some circumstances when clinical patients are used, such as patients who have terminal cancer or HIV and the treatment is to make healthy individuals ill; these studies are conducted in controlled clinics called CPUs, where participants receive 24-hour medical attention and oversight. In addition to the mentioned unhealthy individuals, “patients who have already tried and failed to improve on the existing standard therapies" may participate in phase I trials. Volunteers are paid a variable inconvenience fee for their time spent in the volunteer center.
Before beginning a phase I trial, the sponsor must submit an Investigational New Drug application to the FDA detailing the preliminary data on the drug gathered from cellular models and animal studies. Phase I trials can be further divided: Single ascending dose In single ascending dose studies, small groups of subjects are given a single dose of the drug while they are observed and tested for a period of time to confirm safety. A small number of participants three, are entered sequentially at a particular dose. If they do not exhibit any adverse side effects, the pharmacokinetic data are in line with predicted safe values, the dose is escalated, a new group of subjects is given a higher dose. If unacceptable toxicity is observed in any of the three participants, an additional number of participants three, are treated at the same dose; this is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up. If an additional unacceptable toxicity is observed the dose escalation is terminated and that dose, or the previous dose, is declared to be the maximally
The Oceania Youth Handball Championship is an Under 19 for Boys and Under 18 for Girls handball tournament organised by the Oceania Continent Handball Federation. The winners of these competition qualify for the IHF Men's Youth World Championship and IHF Women's Youth World Championship respectively. For the boys there have only been two tournaments held. In 2007 Australia won and they proceeded to the 2007 Men's Youth World Handball Championship in Bahrain finishing 16th. Australia traveled to Tahiti for the second installment; the hosts won two of the three games to claim the title. The third was won by New Zealand in April 2011, they proceeded to the 2011 Men's Youth World Handball Championship in Argentina finishing 20th. The Cook Islands represented Oceania 2010 World Youth Games in Singapore finishing 6th. Both New Zealand and Australia did not take up their option. After a lengthy lay off, the Championship had its third title in New Caledonia 2018. New Zealand retained their title; the girls first tournament was in 2009 in New Caledonia.
The hosts beat Australia four games to nil but Australia did represent Oceania in the 2010 World Youth Games in Singapore. The second tournament, a decade was again in New Caledonia where the hosts retained their title. Oceania Continent Handball Federation web page Oceania on the International Handball Federation web page
Cleveland is a city in northeast Ohio, US. Cleveland may refer to: Cleveland, Queensland Electoral district of Cleveland Cleveland, Tasmania, a place along the Midland Highway in Tasmania Cleveland, Quebec Cleveland, Nova Scotia An obsolete English term for the Duchy of Cleves Cleveland, Gauteng Cleveland, England, an area and former county in the north east of England Redcar & Cleveland, a unitary authority which covers some of the former county Cleveland Cleveland and Whitby Cleveland Cleveland and Yorkshire North Cleveland and Richmond Archdeaconry of Cleveland Cleveland Hills, a range of hills in North Yorkshire Cleveland, Alabama Cleveland, Arkansas, an unincorporated community in Conway County Cleveland, California Cleveland, Florida Cleveland, Georgia Cleveland, Illinois Cleveland, Indiana Cleveland, Kansas Cleveland, Minnesota, a small city in Le Sueur County Cleveland, Minnesota, a neighborhood Cleveland, Mississippi Cleveland, Missouri Cleveland, New York Cleveland, North Carolina Cleveland, Johnston County, North Carolina Cleveland, North Dakota Cleveland, Oklahoma Cleveland, Tennessee Cleveland, Texas Cleveland, Utah Cleveland, Virginia Cleveland, Washington Cleveland, Chippewa County, Wisconsin Cleveland, Jackson County, Wisconsin Cleveland, Manitowoc County, Wisconsin Cleveland, Marathon County, Wisconsin Cleveland, Taylor County, Wisconsin Cleveland County, Arkansas Cleveland County, North Carolina Cleveland County, Oklahoma Cleveland National Forest, California USS Cleveland, a protected cruiser commissioned in 1903 and scrapped in 1930 USS Cleveland, a light cruiser commissioned in 1942 and active in World War II USS Cleveland, an amphibious transport dock commissioned in 1967 and decommissioned in 2011 SS Cleveland, a steam-powered passenger ship operated by the Hamburg America Line Mount Cleveland, a summit of Chuginadak Island Mount Cleveland, the highest summit of Glacier National Park Cleveland Golf, a U.
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S. warship USS Cleveland Cleaveland Cleveland Township Mount Cleveland Cleveland High School Cape Cleveland Duke of Cleveland, a defunct title in the English and UK's peerage Earl of Cleveland, a defunct title in the English peerage Cleveland Golf, a golfing brand with a number of clubs and apparel Hello Cleveland!, a record label Hot in Cleveland, TV series starring Betty White Cleveland-Cliffs, former name of Cliffs Natural Resources The Cleveland Show, a spin-off of Family Guy Grover Cleveland Alexander, Hall of Fame baseball player