Clinical Research –An outline
Clinical research is an integral part of the drug discovery process to ensure the safety and efficacy of any new drug. In today’s global scientific era, clinical trials are the mainstay for bringing newer and better drugs to market. Although a set of robust guidelines and regulations are in place to govern the conduct of clinical trials in any country, the conduct of clinical research is also looked upon as an area of humanitarian concern.
Discovering and bringing one new drug to the public typically costs a pharmaceutical or biotechnology company nearly $900 million to $1 billion and takes an average of 10 to 12 years. It is designed to ensure that only those pharmaceutical products that are both safe and effective are brought to market.
New drugs begin in the laboratory with scientists, including chemists and pharmacologists, who identify cellular and genetic factors that play a role in specific diseases. Out of every 5,000 new compounds identified during the discovery process, only five are considered safe for testing in human volunteers after preclinical evaluations. After three to six years of further clinical testing in patients, only one of these compounds is ultimately approved as a marketed drug for treatment.
Steps in Drug Discovery & Development (Molecule to Drug)
Target Identification:Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease.
Target Prioritization/Validation: To select targets most likely to be useful in the development of new treatments for disease, researchers analyze and compare each drug target to others based on their association with a specific disease and their ability to regulate biological and chemical compounds in the body. Tests are conducted to confirm that interactions with the drug target are associated with a desired change in the behavior of diseased cells. Research scientists can then identify compounds that have an effect on the target selected.
Lead Identification : A lead compound or substance is one that is believed to have potential to treat disease. Laboratory scientists can compare known substances with new compounds to determine their likelihood of success. Leads are sometimes developed as collections, or libraries, of individual molecules that possess properties needed in a new drug. Testing is then done on each of these molecules to confirm its effect on the drug target.
Lead Optimization : Lead optimization compares the properties of various lead compounds and provides information to help biopharmaceutical companies select the compound or compounds with the greatest potential to be developed into safe and effective medicines. Often during this same stage of development, lead prioritization studies are conducted in living organisms (in vivo) and in cells in the test tube (in vitro) to compare various lead compounds and how they are metabolized and affect the body.
In the preclinical stage of drug development, an investigational drug must be tested extensively in the laboratory to ensure it will be safe to administer to humans. Testing at this stage can take from one to five years and must provide information about the pharmaceutical composition of the drug, its safety, how the drug will be formulated and manufactured, and how it will be administered to the first human subjects.
Preclinical Toxicology : During the preclinical development of a drug, laboratory tests document the effect of the investigational drug in living organisms (in vivo) and in cells in the test tube (in vitro).
Chemistry Manufacturing and Controls (CMC)/Pharmaceutics : The results of preclinical testing are used by experts in pharmaceutical methods to determine how to best formulate the drug for its intended clinical use. Regulatory agencies require testing that documents the characteristics - chemical composition, purity, quality and potency of the drug's active ingredient and of the formulated drug.
Pharmacology/Toxicology: Pharmacological testing determines effects of the candidate drug on the body. Toxicology studies are conducted to identify potential risks to humans.
Results of all testing must be provided to the appropriate regulatory agencies of the respective country in order to obtain permission to begin clinical testing in humans. Regulatory agencies review the specific tests and documentation that are required to proceed to the next stage of development.
Clinical Trial / Research / Testing is usually described as consisting of Phase I, Phase II, Phase III and Phase IV clinical studies. In each successive phase, increasing numbers of patients are tested. There is new trend of Phase 0 has emerged in the last few years as well.
Phase 0 Clinical Studies - Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)'s recent exploratory Investigational New Drug (IND) guidance are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at sub therapeutic doses based on reduced manufacturing and toxicological requirements, allowing the demonstration of drug-target effects and assessment of pharmacokinetic - pharmacodynamic relationships in humans earlier in clinical development. The objectives of a phase 0 cancer clinical trials are to establish at the very earliest opportunity-before large numbers of patients have been accrued and exposed to potential drug-associated toxicity-whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted.
Phase I Clinical Studies: Phase I studies are designed to verify safety and tolerability of the candidate drug in humans and typically take six to nine months. These are the first studies conducted in humans. A small number of subjects, usually from 20 to 100 healthy volunteers, take the investigational drug for short periods of time. Testing includes observation and careful documentation of how the drug acts in the body - how it is absorbed, distributed, metabolized and excreted.
Phase II Clinical Studies: Phase II studies are designed to determine effectiveness and further study the safety of the candidate drug in humans. Depending upon the type of investigational drug and the condition it treats, this phase of development generally takes from six months up to three years. Testing is conducted with up to several hundred patients suffering from the condition the investigational drug is designed to treat. This testing determines safety and effectiveness of the drug in treating the condition and establishes the minimum and maximum effective dose. Most Phase II clinical trials are randomized, or randomly divided into groups,
one of which receives the investigational drug, one of which gets a placebo containing no medication and sometimes a third group that receives a current standard treatment to which the new investigational drug will be compared.
Phase III Clinical Studies: Phase III studies provide expanded testing of effectiveness and safety of an investigational drug, usually in randomized and blinded clinical trials. Depending upon the type of drug candidate and the condition it treats, this phase usually requires one to four years of testing. In Phase III, safety and efficacy testing is conducted with several hundred to thousands of volunteer patients suffering from the condition the investigational drug treats.
New Drug Application (NDA) : NDAs applications to market a new drug. Such applications document safety and efficacy of the investigational drug and contain all the information collected during the drug development process. At the conclusion of successful preclinical and clinical testing, this series of documents is submitted to the applicable regulatory authorities of the countries. The application must present substantial evidence that the drug will have the effect it is represented to have when people use it or under the conditions for which it is prescribed, recommended or suggested in the labeling.
Phase IV Studies: Phase IV trials, which often begin after approval, may supplement or complete earlier trials by providing additional safety data. Phase IV studies expand testing of a proven drug to broader patient populations and compare the long-term effectiveness and/or cost of the drug to other marketed drugs available to treat the same condition. Post-approval studies test a marketed drug in new age groups or patient types. Pharmacovigilance play an important role especially in this stage of study. Some studies focus on previously unknown side effects or related risk factors. As with all stages of drug development testing, the purpose is to ensure the safety and effectiveness of marketed drugs.
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Clinical research is an integral part of the drug discovery process to ensure the safety and efficacy of any new drug. In today’s global scientific era, clinical trials are the mainstay for bringing newer and better drugs to market. Although a set of robust guidelines and regulations are in place to govern the conduct of clinical trials in any country, the conduct of clinical research is also looked upon as an area of humanitarian concern.
Discovering and bringing one new drug to the public typically costs a pharmaceutical or biotechnology company nearly $900 million to $1 billion and takes an average of 10 to 12 years. It is designed to ensure that only those pharmaceutical products that are both safe and effective are brought to market.
New drugs begin in the laboratory with scientists, including chemists and pharmacologists, who identify cellular and genetic factors that play a role in specific diseases. Out of every 5,000 new compounds identified during the discovery process, only five are considered safe for testing in human volunteers after preclinical evaluations. After three to six years of further clinical testing in patients, only one of these compounds is ultimately approved as a marketed drug for treatment.
Steps in Drug Discovery & Development (Molecule to Drug)
Target Identification:Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease.
Target Prioritization/Validation: To select targets most likely to be useful in the development of new treatments for disease, researchers analyze and compare each drug target to others based on their association with a specific disease and their ability to regulate biological and chemical compounds in the body. Tests are conducted to confirm that interactions with the drug target are associated with a desired change in the behavior of diseased cells. Research scientists can then identify compounds that have an effect on the target selected.
Lead Identification : A lead compound or substance is one that is believed to have potential to treat disease. Laboratory scientists can compare known substances with new compounds to determine their likelihood of success. Leads are sometimes developed as collections, or libraries, of individual molecules that possess properties needed in a new drug. Testing is then done on each of these molecules to confirm its effect on the drug target.
Lead Optimization : Lead optimization compares the properties of various lead compounds and provides information to help biopharmaceutical companies select the compound or compounds with the greatest potential to be developed into safe and effective medicines. Often during this same stage of development, lead prioritization studies are conducted in living organisms (in vivo) and in cells in the test tube (in vitro) to compare various lead compounds and how they are metabolized and affect the body.
In the preclinical stage of drug development, an investigational drug must be tested extensively in the laboratory to ensure it will be safe to administer to humans. Testing at this stage can take from one to five years and must provide information about the pharmaceutical composition of the drug, its safety, how the drug will be formulated and manufactured, and how it will be administered to the first human subjects.
Preclinical Toxicology : During the preclinical development of a drug, laboratory tests document the effect of the investigational drug in living organisms (in vivo) and in cells in the test tube (in vitro).
Chemistry Manufacturing and Controls (CMC)/Pharmaceutics : The results of preclinical testing are used by experts in pharmaceutical methods to determine how to best formulate the drug for its intended clinical use. Regulatory agencies require testing that documents the characteristics - chemical composition, purity, quality and potency of the drug's active ingredient and of the formulated drug.
Pharmacology/Toxicology: Pharmacological testing determines effects of the candidate drug on the body. Toxicology studies are conducted to identify potential risks to humans.
Results of all testing must be provided to the appropriate regulatory agencies of the respective country in order to obtain permission to begin clinical testing in humans. Regulatory agencies review the specific tests and documentation that are required to proceed to the next stage of development.
Clinical Trial / Research / Testing is usually described as consisting of Phase I, Phase II, Phase III and Phase IV clinical studies. In each successive phase, increasing numbers of patients are tested. There is new trend of Phase 0 has emerged in the last few years as well.
Phase 0 Clinical Studies - Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)'s recent exploratory Investigational New Drug (IND) guidance are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at sub therapeutic doses based on reduced manufacturing and toxicological requirements, allowing the demonstration of drug-target effects and assessment of pharmacokinetic - pharmacodynamic relationships in humans earlier in clinical development. The objectives of a phase 0 cancer clinical trials are to establish at the very earliest opportunity-before large numbers of patients have been accrued and exposed to potential drug-associated toxicity-whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted.
Phase I Clinical Studies: Phase I studies are designed to verify safety and tolerability of the candidate drug in humans and typically take six to nine months. These are the first studies conducted in humans. A small number of subjects, usually from 20 to 100 healthy volunteers, take the investigational drug for short periods of time. Testing includes observation and careful documentation of how the drug acts in the body - how it is absorbed, distributed, metabolized and excreted.
Phase II Clinical Studies: Phase II studies are designed to determine effectiveness and further study the safety of the candidate drug in humans. Depending upon the type of investigational drug and the condition it treats, this phase of development generally takes from six months up to three years. Testing is conducted with up to several hundred patients suffering from the condition the investigational drug is designed to treat. This testing determines safety and effectiveness of the drug in treating the condition and establishes the minimum and maximum effective dose. Most Phase II clinical trials are randomized, or randomly divided into groups,
one of which receives the investigational drug, one of which gets a placebo containing no medication and sometimes a third group that receives a current standard treatment to which the new investigational drug will be compared.
Phase III Clinical Studies: Phase III studies provide expanded testing of effectiveness and safety of an investigational drug, usually in randomized and blinded clinical trials. Depending upon the type of drug candidate and the condition it treats, this phase usually requires one to four years of testing. In Phase III, safety and efficacy testing is conducted with several hundred to thousands of volunteer patients suffering from the condition the investigational drug treats.
New Drug Application (NDA) : NDAs applications to market a new drug. Such applications document safety and efficacy of the investigational drug and contain all the information collected during the drug development process. At the conclusion of successful preclinical and clinical testing, this series of documents is submitted to the applicable regulatory authorities of the countries. The application must present substantial evidence that the drug will have the effect it is represented to have when people use it or under the conditions for which it is prescribed, recommended or suggested in the labeling.
Phase IV Studies: Phase IV trials, which often begin after approval, may supplement or complete earlier trials by providing additional safety data. Phase IV studies expand testing of a proven drug to broader patient populations and compare the long-term effectiveness and/or cost of the drug to other marketed drugs available to treat the same condition. Post-approval studies test a marketed drug in new age groups or patient types. Pharmacovigilance play an important role especially in this stage of study. Some studies focus on previously unknown side effects or related risk factors. As with all stages of drug development testing, the purpose is to ensure the safety and effectiveness of marketed drugs.
Hey frends kaisa laga.plz comment...ok
aage or bataonga................CRA ke baare me.
