clinical trials

In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study.

Types of clinical trials - The most commonly performed clinical trials evaluate new drugs, medical devices, biologics, or other interventions to patients in strictly scientifically controlled settings, and are required for Food and Drug Administration approval of new therapies. Trials may be designed to assess the safety and efficacy of an experimental therapy, to assess whether the new intervention is better than standard therapy, or to compare the efficacy of two standard or marketed interventions. To be ethical, they must involve the full and informed consent of participating human subjects. They are closely supervised by appropriate regulatory authorities. All interventional studies must be approved by an ethics committee before permission is granted to run the trial.The study design that provides the most compelling evidence of a causal relationship between the treatment and the effect, is the randomized controlled trial. Studies in epidemiology such as the cohort study and the case-control study are clinical studies in that they involve human participants, but provide less compelling evidence than the randomized controlled trial. The major difference between clinical trials and epidemiological studies is that, in clinical trials, the investigators manipulate the administration of a new intervention and measure the effect of that manipulation, whereas epidemiological studies only observe associations (correlations) between the treatments experienced by participants and their health status or diseases.Currently some Phase II and most Phase III drug trials are designed to be randomized, double-blind, and placebo-controlled. This means that each study subject is randomly assigned to receive one of the treatments, which might be the placebo. Neither the subjects nor scientists involved in the study know which study treatment is being administered to any given subject; and, in particular, none of those involved in the study know which subjects are being administered a placebo. Of note, during the last ten years or so it has become a common practice to conduct "active comparator" trials - in other words, when a treatment exists that is clearly better than doing nothing (''i.e.'' the placebo) for the subject, the alternate treatment would be a standard-of-care therapy.While the term clinical trials is most commonly associated with large randomized studies, many clinical trials are small. They may be initiated by single physicians or a small group of physicians, and are designed to test simple questions. Other clinical trials require large numbers of participants followed over long periods of time. It is sometimes necessary to organize multicentre clinical trials. Often the centres taking part in such trials are in different countries (in which case they are termed international clinical trials).The number of patients enrolled in the study also has a large bearing on the ability of the trial to reliably detect an effect of a treatment. This is described as the "power" of the trial. It is usually expressed as the probability that, if the treatments differ in their effect on the outcome of interest, the statistical analysis of the trial data will detect that difference. The larger the sample size or number of participants, the greater the statistical power. However, in designing a clinical trial, this consideration must be balanced with the greater costs associated with larger studies. The power of a trial is not a single, unique value; it estimates the ability of a trial to detect a difference of a particular size (or larger) between the treated and control groups. For example, of a lipid lowering drug with 100 patients per group, might have a power of .90 to detect a difference between active and placebo of 10 mg/dL or more, but only have a power of .70 to detect a difference of 5 mg/dL.

Phases - Drug clinical trials are commonly classified into four phases, and the drug-development process will normally proceed through all four stages over many years. If the drug successfully passes through the first three phases, it will usually be successfully approved for use in the general population.Before embarking on costly clinical trials, Pharmaceutical_companypharmaceutical companies will perform pre-clinical development to ensure that their investment is wise.

Phase I - Phase I trials are the first-stage of testing in human subjects. Normally a small (20-80) group of healthy volunteers will be selected. This phase includes trials designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a therapy. These trials are almost always conducted in an inpatient clinic, where the subject can be observed by full-time medical staff. The subject is usually observed until several half-lives of the drug have passed. Phase I trials also normally include dose-ranging studies such that doses for clinical use can be refined. The tested range of doses will usually be a small fraction of the dose that causes harm in animal testing. Phase I trials most often include healthy subjects. Other groups commonly tested include subjects who are renally or hepatically impaired.Phase I trials of new cancer drugs are a little different. These studies are ususally carried out in patients with advanced (metastatic) cancer. These trials are usually offered to patients who have had other types of therapy and who have few other treatment choices.There are two specific kinds of Phase I trials - SAD studies, and MAD studies.SAD - Single Ascending Dose studies are those in which groups of three or six patients are given a small dose of the drug and observed for a specific period of time. If they do not exhibit any adverse side effects, a new group of patients is then given a higher dose. This is continued until intolerable side effects start showing up, at which point the drug is said to have reached the Maximum tolerated dose (MTD). MAD - Multiple Ascending Dose studies are conducted to better understand the !pharmacokinetics/pharmacodynam ics? of the drug. In these studies, a group of patients receives a low dose of the drug and the dose is subsequently escalated upto a predetermined level. Samples (of blood, and other fluids) are collected at various time points and analyzed to understand how the drug is processed within the body.

Phase II - Once the initial safety of the therapy has been confirmed in Phase I trials, Phase II trials are performed on larger groups (100-300) and are designed to assess clinical efficacy of the therapy; as well as to continue Phase I assessments in a larger group of volunteers and patients. The development process for a new drug commonly fails during Phase II trials due to the discovery of poor efficacy or toxic effects.

Phase III - Phase III studies are large double-blind randomized controlled trials on large patient groups (1000-3000 or more) and are aimed at being the definitive assessment of the efficacy of the new therapy, especially in comparison with currently available alternatives. Phase III trials are the most expensive, time-consuming and difficult trials to design and run; especially in therapies for chronic conditions. Once a drug has proven satisfactory over Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. This collection of information makes up the "regulatory submission" that is provided for review to various regulatory authorities in different countries (such as the Therapeutic Goods Administration (TGA) in Australia, the European Medicines Agency (EMEA) or the FDAFood and Drug Administration (FDA) in the United States) for marketing approval.

Phase IV - Phase IV trials involve the post-launch safety surveillance and ongoing technical support of a drug. Phase IV studies may be mandated by regulatory authorities or may be undertaken by the sponsoring company for competitive or other reasons. Post-launch safety surveillance is designed to detect any rare or long-term adverse effects over a ''much'' larger patient population and timescale than was possible during the initial clinical trials. Such adverse effects detected by Phase IV trials may result in the withdrawal or restriction of a drug - recent examples include cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx).

References -

Rang HP, Dale MM, Ritter JM, Moore PK (2003). ''Pharmacology'' 5 ed. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4

Finn R, (1999). "Cancer Clinical Trials: Experimental Treatments and How They Can Help You." Sebastopol: O'Reilly & Associates. ISBN 1-56592-566-1

See also -

Pre-clinical development

External links -

cancer.gov - What is a Clinical Trial? from National Cancer Institute, US National Institutes of Health

clinicaltrials.gov - ClinicalTrials.gov from US National Library of Medicine

centerwatch.com - Thomson CenterWatch Industry Sponsored Clinical Trial Listings

cochrane.org - The Cochrane collaboration

!globalizationandhealth.com - Can context justify an ethical double standard for clinical research in developing !countries?category:experimenta l? !designcategory:pharmacologycat egory:clinical? !researchCategory:Pharmaceutica l? industryca:Assaig clínicde:Studie (Medizin)es:Ensayo clínicolt:Klinikinis !tyrimasja:治験ru:Клини� �еские? !исследованияhe:נ� �סוי? קליני DEBUG REDIRECT (clinical trial)

Alzheimer's Disease Education and Referral (ADEAR) Center
A service of the Federal Government’s National Institute on Aging, the ADEAR Center provides current, comprehensive Alzheimer’s disease information to patients and families, health care providers, caregivers, and the public. Resources include a toll-free information and referral line (1-800-438-4380), free publications, quarterly newsletter for professionals, and our Web site www.alzheimers.nia.nih.gov.
http://www.alzheimers.nia.nih.gov

Hair transplant instructions
nternational Hair transplant & hair loss institute is The preferred choice to avoid strip Scars by using FIT/FUE & Body Hair techniques solving hair loss permanent, search for information,articles and treatments.
http://www.forhair.com/

PharmiWeb.com
A significant resource for the Pharmaceutical Industry. News, Events, Jobs, resources.
http://www.pharmiweb.com/

Innovative Medical Recruiting, LLC
Full service medical, pharmaceutical, biotechnology recruitment firm, based in the US.
http://www.innomedical.com/

ContractPharm, an agency-independent resource for pharmaceutical research contractors.
ContractPharm - A one-stop shop for pharmaceutical clinical contractors. We have various resources for contractors including contracting advice, CV advice, clinical advice, tips on dealing with agencies and a vocal forum. when contractors are are looking to to enter the contract market, wondering how to start contracting or are simply looking for your next position, they''ll find everything they need here. We also have a significant links menu, providing our visitors with the best sites, for travel and shopping online.
http://www.contractpharm.co.uk/

medicomp GmbH
medicomp Gesellschaft für Versuchsplanung und Datenanalyse mbH CRO in München
http://www.medicomp-cro.de/

Fibroid Network Charity
New Medical, surgical & Natural Fibroid Treatments, Discussion Groups, Worldwide Fibroids resources
http://www.fibroidnetworkonline.com/

American Association of Nurse Anesthetists Online
The AANA, American Association of Nurse Anesthetists, promotes the safe administration of anesthesia, as well as information on the history of nurse anesthesia, and how to become a nurse anesthetist. There also is a Public Information and Resources section for patients about to undergo surgical procedures.
http://www.aana.com/

Manitoba Prostate Cancer Support Group
The Manitoba Prostate Cancer Support Group provides support and information on Cancer prevention and treatment options.
http://www.manpros.org/

Data Mining International
Data Mining International is a swiss company specialized in modeling and data mining of various databases to extract or simulate meaningful information. Main applications are customer databases, clinical trials, forecasting, economic modeling and simulations in various areas.
http://www.datamining-international.com/

CenterWatch: Clinical Trials Listing Service
Listing of clinical research trials, information about physicians and medical centers performing clinical research and drug therapies newly approved by the FDA.
http://www.centerwatch.com/

ClinicalTrials.Gov
Searchable database which provides patients, family members and the public with information about current ongoing clinical research studies. From the U.S. National Library of Medicine.
http://clinicaltrials.gov

National Cancer Institute
The U.S. National Institute of Health's cancer research wing.
http://www.nci.nih.gov/

ACTIS: Clinical Trials for AIDS
World-wide resources about trials in study against acquired immune deficiency syndrome.
http://www.actis.org/