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38 Cards in this Set
- Front
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Nuremberg Code Date Resulted from? Created the first principles of research: |
1947 Resulted from “medical experiments” in the Nuremberg Trials where most prisoners died or were permanently crippled as a result of the experiments Created the first principles of clinical research: animal experiments and knowledge of the history of the disease Beneficence towards participants |
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Nuremberg Code Degree of risk should not exceed? What should be provided to project who against what? What must the physician in charge be prepared to do? |
Degree of risk should not exceed humanitarian importance Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death Physician in charge must be prepared to terminate the experiment at any stage, if he/she has probably cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him/her that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject |
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Declaration of Helsinki Date Created by Built upom Further focus on How many revisions has it gone through? What is it considered as?
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Created by World Medical Association Built upon the Nuremberg Code Further focus on clinical research Gone through 7 revisions, most current 2013 Considered the cornerstone document of human research ethics and designed from a clearly formulated protocol |
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Declaration of Helsinki Who should informed consent be obtained from? Protocols should be reviewed by... Human subject research should be based on results from... Who should conduct the research? What is a must? Risk should not exceed? |
Informed consent must be obtained from subject or legal guardian Protocols should be reviewed by an independent committee Human subject research should be based on results from laboratory and animal research Research should be conducted by a medically qualified person Informed consent is a must Risk should not exceed the benefits |
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Belmont Report Date Estab. ____ fundamental ____ principles Describe them |
Established three fundamental ethical principles: Respect for Persons: Individual autonomy - Beneficence - Maximize benefits and minimize harm - Respecting decisions - Securing well-being - Justice - Equitable distribution of research costs and benefits - Participants should be treated equally - Selection based on reason related to study |
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Belmont Report What did it do? What did it led to the estab. of? Led to the creation of? |
Expanded and revised regulations that protect human research subjects in the United States Led to the establishment of the Office of Human Research Protection (OHRP) Led to the creation of the Institutional Review Board (IRB). |
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Clinical research determines: Clinical research can also include:
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- Safety and effectiveness - Involves collection of biological specimens on human subjects
- Behavioral studies & Surveys |
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What Defines A Human Subject? FDA and HHS definitions |
FDA defines Human Subject as an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. Health and Human Services (HHS) Regulations - "Human subject" means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information. |
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Clinical Trial A clinical trial is also known |
as an Interventional Study. |
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National Institutes of Health (NIH) organizes trials into five different types:
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• Treatment trials - Most trials fall under this category • Prevention trials - Look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning Diagnostic trials-conducted to find better tests or procedures for diagnosing a particular disease or condition. Screening trials -examine methods of identifying a condition(or risk factors for a condition) in people who are not yet known to have the condition (or risk factor). Quality of life trials - explore ways to improve comfort and the quality of life for individuals with a chronic illness |
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Clinical Trial – Protocol written by? Which CFR defines sponsor and sponsor investigator? |
• PI Initiated: • Sponsor Initiated: • "Sponsor" and "sponsor-investigator" are defined at 21 CFR 312.3(a) |
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Drug Development To identify substances that has a desirable therapeutic effect in a process known as ____________. Demonstrate that a particular _______ is relevant to the disease being studied in both _______ and in _______ of disease. Prove that the compound does not cause _______ and is _______. |
To identify substances that has a desirable therapeutic effect in a process known as classical pharmacology. Demonstrate that a particular target is relevant to the disease being studied in both living cells and in animal models of disease. Prove that the compound does not cause chromosomal damage and is not toxic. |
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Drug Development How it is ____________ Best ____________ in the body Does it metabolize ____________ and ____________ Is it ____________ from the body and Demonstrate not to be ____________ |
How it is absorbed Best distribution in the body Does it metabolize efficiently and effectively Is it excreted from the body and Demonstrate not to be toxic |
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Drug Development ICH ? This was developed to help protect __________ and _______ receiving __________ from potential _______ effects of pharmaceuticals It also helped to avoid unnecessary use of __________ and other __________. |
Safety Pharmacology Studies for Human Pharmacology This was developed to help protect human subjects and patients receiving marketed products from potential adverse effects of pharmaceuticals It also helped to avoid unnecessary use of animals and other resources. |
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What is an IND? The __________ (IND) is a request for authorization from the __________ to administer an __________ or __________ product to humans. __________ and __________ are synonymous Federal law requires approved __________ before crossing state lines There is a ___ calendar day waiting period for the FDA to review the IND before initiating any clinical trial. |
The Investigational New Drug (IND) is a request for authorization from the Food and Drug Administration to administer an investigational drug or biological product to humans. Investigational drug and investigational new drug are synonymous Federal law requires approved marketing application before crossing state lines There is a 30 calendar day waiting period for the FDA to review the IND before initiating any clinical trial. |
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What is an IND? Please review 21 CFR 312.23 and 312.40 INVESTIGATIONAL NEW DRUG APPLICATION Even though the US specific terms for applications (IND, NDA) are not used in non-US countries, the process is similar. The sponsor is to initiate the IND by submitting a form ___: Investigation New Drug Application which must contain:
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Even though the US specific terms for applications (IND, NDA) are not used in non-US countries, the process is similar. The sponsor is to initiate the IND by submitting a form 1751: Investigation New Drug Application which must contain: Cover sheet Investigator brochure Protocol |
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What is an IND? There are three IND types: In accordance with 21CFR, Sec. _____, or Sec. _____ |
An Investigator IND Treatment IND Emergency Use IND In accordance with 21CFR, Sec. 312.23, or Sec. 312.34 |
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What is an IND – Expanded Access In August ______ FDA amended it’s IND rules to include: Expanded Access for Treatment Use - Availability is limited by a ______ (?) when the primary purpose is to ______, ______, or ______ a patient’s disease or condition. Please review 21CFR312.300 |
In August 2009 FDA amended it’s IND rules to include: Expanded Access for Treatment Use - Availability is limited by a Risk Evaluation and Mitigation Strategy (REMS) when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition.
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What is an IND – Expanded Access Expanded access to investigational drugs for treatment used will be available to: Immediately __________ or ________, and there is no comparable or satisfactory _________ The ________ justifies the potential _______ The investigational drug will not interfere with completion of _______ |
Expanded access to investigational drugs for treatment used will be available to: Immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy The benefit justifies the potential risks The investigational drug will not interfere with completion of clinical investigations |
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What is an IND – Expanded Access Expanded Access Submission Required for ________ type May require a new ________ Goes into effect ________ days after FDA received the IND or on ________ by ________ Investigators must report ________ to the ________, ensure that ________ is obtained and approved by IRB ________ how the expanded access use will meet the ________ and must agree to submit an ________ submission within _____ days of FDA’s authorization of use. |
Expanded Access Submission Required for each type May require a new IND Goes into effect 30 days after FDA received the IND or on notification by FDA Investigators must report adverse drug events to the sponsor, ensure that informed consent is obtained and approved by IRB Explanation how the expanded access use will meet the requirements and must agree to submit an expanded access submission within 15 days of FDA’s authorization of use. |
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Clinical Investigation of a Drug That is Exempt From the IND Requirements: Must meet all of the following requirements: • The investigational drug is _________ in the US • The investigation is not intended to be reported to the _________ as a _________ study in support of a _________ for that product • The investigation is not intended to support a _________ in _________ to an existing lawfully marketed prescription drug product The investigation does not involve a route of _________ or _________ or use in a patient population or other factor that significantly _________ the risks (or _________ the acceptability of the risks) associated with the use of the drug product. The investigation will be conducted in compliance with the requirements for institutional review set forth in FDA regulations ___ CFR ___, and requirements for _________ as set forth in FDA regulations ___ CFR ___
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• The investigational drug is lawfully marketed in the US Must meet all of the following requirements: • The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for that product • The investigation is not intended to support a significant change in advertising to an existing lawfully marketed prescription drug product The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product. The investigation will be conducted in compliance with the requirements for institutional review set forth in FDA regulations 21 CFR 56, and requirements for informed consent as set forth in FDA regulations 21 CFR 50
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Clinical Investigation of a Drug That is Exempt From the IND Requirements • The investigation will be conducted in compliance with FDA regulations 21 CFR ______: ______ and ______ for investigational drugs. Thorough documentation is required to support this exemption criterion and may include prior ______ or other public ______. If such evidence cannot be provided, a physician should submit a research ______ (limited in scope) to the FDA. The physician is now considered a ______. |
Theinvestigationwillbeconductedincompliance with FDA regulations 21 CFR 312.7: Promotion and charging for investigational drugs. Thorough documentation is required to support this exemption criterion and may include prior publications or other public disclosures. If such evidence cannot be provided, a physician should submit a research IND (limited in scope) to the FDA. The physician is now considered a sponsor-investigator. |
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What is an NDA Types of Applications: NDA ANDA OTC "Applicant" is defined in 21 CFR 314.3 |
New Drug Application (NDA) Abbreviated New Drug Application (ANDA) Over-the-Counter Drugs (OTC) "Applicant" is |
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An IND may be submitted for one or more phases of an investigation. |
True |
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Phases of a Clinical Trial Phase 0: Exploratory study involving very limited _______ exposure to the drug, with no ________ or ________ goals. Provides no ________ or ________ data Usually involves ________ subjects. |
Phase 0: Exploratory study involving very limited human exposure to the drug, with no therapeutic or diagnostic goals. Provides no safety or efficacy data Usually involves 10-15 subjects. |
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Phases of a Clinical Trial Phase I: Studies that are usually conducted with ________ and that emphasize ________. • Ranges from ________ to ________ subjects ________. |
Phase I: Studies that are usually conducted with healthy volunteers and that emphasize safety. • Ranges from 20 to 80 subjects effectiveness. |
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Phase III – Final confirmation of ________ and ________. Monitor ________ and collect information for ________ approval. This is usually ranges from ________ to about ________ subjects. Phase IV – ________ studies during ________ – This occurs ________ FDA approval. Gathers ________ information about the drug. |
Phase III – Final confirmation of safety and efficacy. Monitor side effects and collect information for FDA approval. This is usually ranges from several hundred to about 3,000 subjects. Phase IV – Sentry studies during sales – This occurs after FDA approval. Gathers additional information about the drug. |
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Overall Drug Development Clinical phases require ________ years Filing for ________ Additional ________ studies Overall takes an average of between ________ years. |
Clinical phases require 1, 2, and 3 years Filing for NDA Additional post marketing studies Overall takes an average of between 8 – 12 years. |
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Definition : Sponsor Definition from FDA 21 CFR Part 312.3 The sponsor may be an __________ or__________, __________ agency, __________, __________, or __________ organization. The sponsor does not actually __________ the investigation unless the sponsor is a __________. A person other than an individual that uses one or more of its own __________ to __________ an investigation that it has initiated is a sponsor, not a __________, and the employees are __________. |
A person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators. |
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Definition : Sponsor **Guiding Principle**: The creator or author of the ___________ who takes ultimate ___________ for the study. Investigator Initiated or Hypothesis Driven Investigator Initiated Studies • The Principal Investigator is the sponsor because they ___________ the protocol. • National Institutes of Health (NIH), National Science Foundation (NSF), Industry Partner, or Agency would be the ___________ source for these protocols. |
**Guiding Principle**: The creator or author of the protocol who takes ultimate responsibility for the study. Investigator Initiated or Hypothesis Driven Investigator Initiated Studies • The Principal Investigator is the sponsor because they authored the protocol. • National Institutes of Health (NIH), National Science Foundation (NSF), Industry Partner, or Agency would be the funding source for these protocols. |
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Definition : Sponsor Industry Initiated Protocols as well as developed the _______ or ______ to be tested. |
Industry Initiated Protocols as well as developed the drug or device to be tested. manufacturing, and testing of the product in people. |
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Roles and Responsibilities of the Sponsor The creator or author of the protocol takes ultimate _________ for the protocol . Keeps the investigators informed of _________ about the drug or device • Especially _________ that occur at other sites. Provides _________ of the trial • _________ the clinical trial Provides _________ needed for the clinical trial _________ data _________ the trial _________ all procedures and data submitted to support the application for approval from the Government |
The creator or author of the protocol takes ultimate responsibility for the protocol . Keeps the investigators informed of new information about the drug or device • Especially Adverse Events that occur at other sites. Provides management of the trial • Designs the clinical trial Provides materials needed for the clinical trial Collects data Monitors the trial Audits all procedures and data submitted to support the application for approval from the Government |
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Definition: Principal Investigator (PI) The Principal Investigator (PI) has the primary responsibility for the ________, ________, and ________ conduct of the protocol. The PI must personally ________ in the project to a significant degree. PI is the title recognized by our Sponsored Projects office as the individual with primary responsibility for a grant or contract. |
The Principal Investigator (PI) has the primary responsibility for the scientific, technical, and administrative conduct of the protocol. The PI must personally participate in the project to a significant degree. PI is the title recognized by our Sponsored Projects office as the individual with primary responsibility for a grant or contract. |
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Roles and Responsibilities of the Principal Investigator and Lead Researcher Assumes overall responsibility for the __________ of the study. Assigns __________ for other members of the team. Ensures that __________ is properly obtained from the study volunteers. Ensures the __________ of the data that are submitted Liaison for major patient care __________ with the __________ and the __________ and ensures that the IRB is informed of all __________ issues. Performs the __________ assessments. |
Assumes overall responsibility for the management of the study. Assigns responsibilities for other members of the team. Ensures that informed consent is properly obtained from the study volunteers. Ensures the accuracy of the data that are submitted Liaison for major patient care issues with the sponsor and the IRB and ensures that the IRB is informed of all safety issues. Performs the medical assessments. |
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Roles and Responsibilities of the Sub-investigators (Co-investigators) Assume the responsibility for _________ assessments. Do not generally have the _________ responsibilities like the Principal Investigator. |
Assume the responsibility for patient care assessments. Do not generally have the administrative responsibilities like the Principal Investigator. |
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Definition: Clinical Research Coordinator (CRC) An individual that handles the _________ and _________ responsibilities of a clinical trial and acts as a _________ for the clinical site. This person may _________ the data or _________ it before it is entered into a study database. |
An individual that handles the administrative and day-to-day responsibilities of a clinical trial and acts as a liaison for the clinical site. This person may collect the data or review it before it is entered into a study database. |
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Roles and Responsibilities of the Clinical Research Coordinator (CRC) Assists in evaluating new protocols for __________ at the site • Industry Sponsored Studies – This would occur when the PI is determining if they would like to __________ in the clinical trial • NIH Studies preparing a grant to submit to the NIH or other granting agency Prepares the site for conducting the study • ______ study staff Participates in the ______ process |
Assists in evaluating new protocols for feasibility at the site • Industry Sponsored Studies – This would occur when the PI is determining if they would like to participate in the clinical trial • NIH Studies preparing a grant to submit to the NIH or other granting agency Prepares the site for conducting the study • Training study staff Participates in the informed consent process |
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Roles and Responsibilities of the Clinical Research Coordinator (CRC) Manages study ________ throughout the study • ________ and ________ subjects • Ensuring that all necessary data is ________ and ________ on the appropriate forms Maintains regular communications with the ________ and ________ Coordinates with the other ________ (Laboratory, Pharmacy, etc.) Coordinates ________ and/or regulatory ________ Professionally ________ the site – ________ contact |
Manages study conduct throughout the study • Contacting and screening subjects • Ensuring that all necessary data is collected and recorded on the appropriate forms Maintains regular communications with the sponsors and institution Coordinates with the other departments (Laboratory, Pharmacy, etc.) Coordinates sponsor and/or regulatory audits Professionally represents the site – primary contact |
