copied cards Flashcards
What does 21 CFR Part 11 cover?
Electronic Records; Electronic Signatures
What is a closed system?
An environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system.
What is an open system?
An environment in which system access is NOT controlled by persons who are responsible for the content of electronic records taht are on the system.
What is a digital signature?
It is an electronic signature based on crypotgraphic methods of originator authentication, computer by using a set of rules and set of parameters such that the identity of the signer and the integrity of the data can be verified.
What is an electronic signature?
it is a computer data compilation of any symbol or series of symbols executed, adopted, or digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
What is a handwritten signature?
a scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in a permanent form.
What does biometrics mean?
it is a method of verifying an individual’s identity based on measurement of the individual’s physical features or repeatable actions wehre those features and/or actions are both unique to that individual and measureable.
Act means…
The Federal Food, Drug, and Cosemetic Act
Agency means…
Food and Drug Administration
General Requirements for electonric signatures are..
1) Each electronic signature should be unique & shall not be reused or reassigned to anyone else. 2) Before the organization certifies the signature they have to verify the identity of the individual. 3) Persons shall certify that electronic signatures used after 20AUG1997 are legally binding.
Electronic signatures NOT based on biometrics shall
1) employ at least two distinct identification components (ID code and password). 2) be used only by genuine owners. 3) use of the signature by anyone other than its genuine owner requires collaboration of two or more individuals.
Electronic signatures that ARE based on biometrics shall
be designed to ensure that they cannot be used by anyone other than their genuine owner.
Controls for ID codes and passwords shall include these 5 components:
1) maintain the uniqueness of each ID code and pw 2) Ensure that the ID code and pw ussuances are periodically checked, recalled, or revised. 3) Following loss management procedures to electronically deauthorize lose, stolen, missing or otherwise potentially compromised tokens, cards, and other devices. 4) use of transaction safeguards to prevent unauthorized use of pws and/or ID codes 5) initial and periodic testing of devices that bear or generate id code or pw info.
What does 21 CFR Part 50 cover?
Protection of Human Subjects
Clinical Investigation means..
any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the FDA or is not subject to requirements for prior submission to the FDA but the results of which are intended to be submitted later to or held for inspection by the FDA as part of an application for a research or marketing permit.
Sponsor
person who initiates a clinical investigation, but who does not actually conduct the investigation.
Sponsor-Investigator
individual who both initiates and actually conducts, alone or with others, a clinical investigation.
Exceptions from informed consent for emergency research
1) subject is in a life-threatening situation and collection of valid scientific evidence is necessary to determine safety and effectiveness of particular interventions. 2) Obtaining consent is not feasible. 3) Participation in the research holds out the prospect of direct benefit. 4) The clinical investigation could not practicably be carried out without the waiver. 5) the tx plan makes sense and the investigator is doing what he/she can to contact a legally authorized rep. 6) IRB has approved 7) additional protections of the rights and welfare of the subjects will be provided
Elements of informed consent
1) statement that the study involved research. 2) description of any reasonably foreseeable risks or discomforts to the subject. 3) description of any benefits to the subject or others. 4) disclosure of alternative procedures. 5) statement describing the extent to which confidentiality of records will be maintained 6) statement regarding compensation and medical tx if any injury. 7) who to contact for answers to pertinent questions about research and subjects rights. 8) participation is voluntary.
Additional elements of informed consent
1) statement that the particular tx may involve additional risk to the subject. 2) anticipated circumstances under which participation may be terminated. 3) any additional costs. 4) consequences of a subjects decision to withdraw. 5) statement that significant findings during the research will be provided. 6) approximate number of subjects involved in the study.
Each IRB should have at least how many members?
5
Each IRB shall include:
1 member whose primary concerns are in the scientific area and 1 whose primary concerns are in nonscientific areas, and 1 who is not otherwise affiliated with the institution.
Criteria for IRB approval
- Risks to subjects are minimized. 2. Risks to subjects are reasonable in relation to anticipated benefits. 3. Selection of subjects is equitable. 4. informed consent from each subject. 5. informed consent should be documented. 6. research plan makes adequate provision for monitoring the data collected. 7. adequate provisions to protect the privacy of subjects and to maintain confidentiality of subjects.
test article
any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354-360F of the public health service act.
A research permit under section 505(i) of the act is usually known as
investigational New Drug (IND) application
A research permit under section 520(g) of the act is usually known as
investigational device exemption (IDE)
When must an IRB register?
Each IRB must submit an initial registration and must renew every 3 years. IRB registration become effective after review and acceptance by HHS.
Where can an IRB register?
Either electronically or in writing to the Office of Good Clinical Practice, Office of Special medical programs, Food and drug administration, silver spring, MD.
How does an IRB revise its registration information?
must submit changes within 90 days. 30 days if disbanning, otherwise at time of registration renewal.
What does 21 CFR Part 312 cover?
Investigational New Drug Application
clinical investigation of a drug product that is lawfully marketed in the US is exempt from the requirements of this part if all of the following applies:
- The investigation is not intended to be reported to the FDA as a well-controlled study in suppport of a new indicatino for use nor intended to be used to support any other significant change in the labeling of the drug. 2) If the drug that is undergoing investiagtion is lawfully marketed as a prescription drug product, the investigation is not intended to support a significnat change in the advertising for the product. 3) 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 associated with the use of the drug product. 4) Investigation is conducted in compliance w/ the IRB and appropriately consents. 5) Investigation is conducted in compliance with the requirements.
What products are exempt from requirements of 312?
1) blood grouping serum 2) reagent red blood cells, and 3) anti-human globulin.
What type of drug is exempt from requirements of 312?
a drug intended solely for tests in vitro or in laboratory research animals.
A clinical investigation involving use of THIS is exempt from the requirements of 312 if the investigation does not otherwise require submission of an IND
Placebo.
Bioavailability studies
YES is subject to provisions of 320.31
Unlabeled indication
No, does not apply to the use in the practice of medicine for an unlabeled indication of a new drug product
Independent ethics committee (IEC)
a review panel that is responsibile for ensuring the protection of the rights, safety, and well-being of human subjects involved in a clinical investigation and is adequately consititued to prvode assurance of that protection.
Investigational new drug
a new drug or biological drug that is used in a clinical investigation.
What does 21 CFR Part 56 cover?
Institutional Review Boards
What is CFR 21 Part 812
Investigational Device Exemptions
What is a significant risk device?
A device that: 1) is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; 2) Is purpoted or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject. 3) is for a use of substantial importance in diagnosising, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject. or 4) Otherwise presented a potential for serious risk to the health safety, or welfare of a subject.
What is a transitional device?
a device subject to 520(l) of the act that is a device that FDA considered to be a new drug or antiboitic before MAY 28 1976.
What is a device?
A device, other than a transitional device, in commercial distribution immediately before May 28 1976 when used for investigated in accordance with the indications in labeling in effect at that time.
Investigational Plan should include:
a) purpose b) protocol c) risk ananlysis d) description of device e) monitoring procedures. f) labeling g consent materials h) IRB information i) Other institutions j) additional records and reports.
What types of changes would require a supplemental application?
1) Changes in investigational plan 2) Changes effected for emergency use 3) Changes effected with notice to FDA within 5 days. 4) Changes submitted in annual report.
Can a sponsor make certain changes without prior approval of a supplemental application?
Yes – but the sponsor must notified the FDA within 5 days of the changes going in to effect.
What types of changes can the sponsor make w/o prior approval on a supplemental application?
1) Developmental changes, including manufacturing changes that do not constitute a significant change in design or basic operation and are made based on basic information gathered during the investigation. 2) Changes to clinical protocol that do not affect validity of data, scientific soundness, or the rights safety, and welfare of human subject. 3) Definition of credible information 4) Notice of IDE change
What are the responsibilities of Sponsors as outlined in subpart C?
1) Gaining FDA and IRB approval before beginning the investigation 2) Selecting investigators and monitors 3) Informing investigators 4) monitoring investigations 5) Emergency Research
Responsibilities of Investigators as outlined in subpart E
1) Awaiting approval. 2) Compliance. 3) Supervising device use. 4) Financial disclosure. 5) Disposing of device.
What does 45 CFR Part 46 cover?
Protection of Human Subjects
dead fetus
a fetus that exhibits neither a heartbeat, spontaneous respiratory activity, movement of voluntary muscles, nor pulsation of the umbilical cord.
fetus
the product of conception from implantation until delivery
nonviable neonate
neonate after delivery that, although living, is not viable.
assent
a child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.
how often must an IRB renew its registrations?
Every 3 years.
When must IRB informatino be updated?
1) Registration info for an IRB must be updated w/in 90 days after changes occur regarding the contact person who provided the RIB registration information or the IRB chairperson. 2) Any renewal or update that is submitted to, and accepted by, OHRP begins a new 3 year effective period. 3) an institution’s decision to disband a registered IRB which it is operating also must be reported to OHRP in writing w/in 30 days after permanent cessation of the IRB’s review of HHS conducted or supported research
FDA Form 482
Notice of Inspection
FDA Form 483
Inspectional Observations
FDA Form 1572
Statement of Investigator
FDA Form 3454
Certification – Financial Interests and Arrangements of Clinical Investigators
FDA Form 3455
Disclosure – Financial Interests and Arrangements of Clinical Investigators.
FDA Form 3500
For Voluntary Reporting of Adverse Events and Product Problems.
FDA Form 3500A
For use by User-Facilities, Distributors, and Manufacturers for Mandatory Reporting.
Which act was signed in to law in 1974
The National Research Act
The National Research Act
created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.
What is the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research charged with?
To identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles.
What is the purpose of the Belmont Report?
It sumarizes the basic ethical principles identified by the Commission in the course of its deliberations.
What are the three basic ethical principles?
1) Respect for persons, 2) Beneficience, and 3) Justice
What are the three applications of the Belmont Report?
1) Informed Consent, 2) Assessment of Risk and Benefits, and 3) Selection of Subjects.
What is the purpose of medical or behavioral practice?
To provide diagnosis, preventive treatment or therapy to particular individuals.
What does research designate?
It designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge.
What two ethical convictions does Respect for Persons incorporate?
1) Individuals should be treated as autonomous agents and 2) persons with dimished autonomy are entitled to protection.
What does it mean to provide beneficience?
It means that we must treat persons in an ethical manner not only be respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being.
What two general rules have been formulated as complementary expressions of beneficient actions?
1) do not harm and 2) maximize possible benefits and minizmie possible harm.
When does an injustice occur?
When some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly.
Applications of the general principles to the conduct of research leads to consideration of the following requirements:
1) Informed consent, 2) risk/benefit assessment, and 3) selection of subjects of research
Informed Consent
Respect for persons requires that subjects, to the degree that they are eligible, be given the opportunity to choose what shall or shall not happen to them.
Respect for person during informed consent is provided when adequate standards for informed consent are satisfied. What are the three standars of informed consent?
1) Information, 2) Comprehension, and 3) Voluntariness.
Since 1945, various codes for the proper and responsible conduct of human experimentation in medical
research have been adopted by different organizations. The best known of these codes are:
1) The Nuremberg Code of 1947, 2) The Helsinki Declaration of 1964, 3) the 1971 Guidelines issued by the US Department of Health, Education, and 4) Welfare Codes for the conduct of social and behavioral research, such as, American Psychological Assocation published in 1973.
What is the Nuremberg Code?
It is a set of ten ethical principles for human experimentation developed in 1947. The code came about as a result of trials held in Nuremberg, Germany at the end of WWII which involved medical professionals accused of murder and torture in the conduct of medical experiments on prisoners of concentration camps.
Name the 10 ethical principles for human experimentation as outlined in the Nuremberg code. (1-4)
#1 Voluntary consent is absolutely essential. #2 The experiment should yield fruitful results for the good of society, unprocurable by other methods or means of study and not random and unnecessary in nature. #3 The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problems under study that the anticipated results will justify the performance of the experiment. #4 The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
Name the 10 ethical principles for human experimentation as outlined in the Nuremberg code. (5-7)
#5 No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; EXCEPT (what??) in experiments where the experimental physicians also serve as subjects. #6 The degree of risk should never exceed that determined by the humanitarian importance of the problem to be solved by the experiement. #7 Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
Name the 10 ethical principles for human experimentation as outlined in the Nuremberg code. (8-10)
#8 The experiment should be conducted only be scientifically qualified persons. #9 During the course of the experiment the human subject should be at liberty to bring the experiment to an end if it has reached the physical or mental state where continuation of the experiment seems to him to be impossible. #10 During the course of the experiment the scientists in charge must be prepared to terminate the experiment at any stage, if he has probably cause to believe in the exercise of the good faith, superior skill and careful judgement required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.
What year was the Nuremberg written?
1947
What are two other publicized examples of ethical abuses in research?
Willowbrook studies (1956-1970) & Jewish Chronic Disease Hospital Study (1963).
What was the atrocity of the Willowbrook Studies?
Children with intellectual disabilities were deliberately infected with the hepatitis virus.
What was the atrocity of the Jewish Chronic Disease Hospital Study?
live cancer cells were injected into 22 cognitively impaired patients.
When was the Tuskegee Syphillis Study?
1932-1972
What was the problem with the Tuskegee Syphillis Study?
Black American men were unknowing subjects in the study; they were not told that they had syphillis, nor were they offered effective treatmetn when it became availabile in the late 1940s (penicillin)
In response to the public concern about the ethics of the Tuskegee Syphillis Study, prisoner research, Willowbrook, and other abuses hearings on “Quality of health Care– Human Experimentation” were held before the Subcommittee on health of the US Senate Committee on Labor and Public Welfare (commonly referred to as the “Kennedy Hearings”) in 1973. What act was passed because of these hearings?
The 1974 National Research Act.
What are the two major provisions of the National Research Act relevant to human subjects research?
1) It esablished the “National Commission for the Protection of Human Subjects of Biomedical adn Behavioral Research” to identify the basic ethical principles underlying human subjects research and develop guidelines for ensuring that human subjects research is conducted according to those guidelines.
2) It required the establishedment of IRBs at organizations receiving Public Health Services support for human subjects research.
The National Commission met from 1975-1978 and issued a series of reprots on vulnerable populations, psychosurgery, IRBs, and other topics that included recommendations for regulating human subjects research. A final report was publichsed in 1979 and is commonly referred to as?
The Belmont Report
What is the World Medical Association Declaration of Helsinki?
Originally adopted in June 1964, it is a set of ethical principles for medical research involving human subjects. It has been amended a number of times since the original adoption; most recently by the WMA in October 2013
Who is the WMA Declaration of Helsinki primarily addressed to?
Physicians – however the WMA encourages others who are involved in medical research with human subjects to adopt these principles.
What topics does the DoH address?
- Risks, Burdens, & Benefits. 2. Vulnerable Groups and Individuals. 3. Scientific Requirements and Research Protocols. 4. Research Ethics Committees. 5. Privacy and Confidentiality. 6. Use of Placebo. 7. Post Trial Provisions 8. Reserach Registration adn Publication and Dissemination of Reults. 9. Unproven Interventions in Clinical Practice. oh woops and I almost forgot: 10. Informed Consent
What year was the Declaration of Helsinki created?
1964
What is the ICH?
International Council for Harmonisation.
ICH Harmonised Guideline for Good Clinical Practice
finalized in November 2016 – the Good Clinical Practices document describes the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors and IRBs.
What does GCP cover?
Aspects of monitoring, reporting and archiving of clinical trials and incorporating addenda on the Essential Documents and on the Investigators Brochures which had been agreed earlier thorugh the ICH process.
What is GCP?
An international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.
What is the objective of this ICH GCP?
To provide a unified standard for the European Union, Japan, and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.
Adverse Drug Reaction
All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.
Adverse Event
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product.
Audit
Systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor’s standard operating procedures, GCP, adn the applicable regulatory requirements.
Comparator (Product)
An investigational or marketed product, or placebo, used as a reference in a clinical trial.
Compliance
Adherence to all the trial-related requiremetns, good clinical practice requirements, adn the applicable regulatory requirements.
Confidentiality
Prevention of disclosure, to other than authorized individuals, of a sponsor’s proprietary information or of a subject’s identity.
Coordinating Committee
A committee that a sponsor may organize to coordinate the conduct of a multicenter trial.
Coordinating Investigator
An investigator assigned the responsibility for the coordination of investigators at different centers participating in a multicenter trial.
Contract Research Organization (CRO)
A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions.
Direct Access
Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial.
Inspection
The act by a regulatory authority of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authorities to be realted to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organization’s facilities, or at other establishments deemed appropriate by the regulatory authorities.
What year did the ICH develop GCP guidelines?
1996
Adverse Event (or Adverse Experience)
any unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Adverse Drug Reaction (ADR) definition #1
All noxious and unintended responses to a medicinal product related to any dose. “responses to medicinal product” means that a causal relationship between medicinal product and AE is at least possible.
Adverse Drug Reaction (ADR) definition #2 (WHO definition)
A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function.
side effect
This term is NOT to be used synonymously with “adverse event” as a side effect can be both negative and positive.
SERIOUS adverse event (experience) or reaction
any untwoard medical occurrence that at any dose level 1) results in death 2) is life-threatening. In this context life-threatening would require inpatient hospitalization or prolongation of existing hospitalization, results in persisent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Serious vs Severe
NOT to be used synonymously. Severe is often used to describe the intensity of a specific event (as in mild, moderate, or severe mycoardial infarction); the event iteself, however, may be or relatively minor medical significance (such as a severe headache). This is NOT the same as “serious” which is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient’s life or functioning.
Reporting Time Frames
Fatal or Life-Threatening Unexpected ADRs: no more than 7 calendar days.
All Other Serious, Unexpcted ADRs: No more than 15 calendar days.
