SOCRA CERIFICATION EXAM 2024, Exams of Nursing

Download SOCRA CERIFICATION EXAM 2024 and more Exams Nursing in PDF only on Docsity! 1 | P a g e SOCRA CERIFICATION EXAM 2024 WITH ACTUAL CORRECT QUESTIONS AND VERIFIED DETAILED ANSWERS BY EXPERTS |FRENQUENTLY TESTED QUESTIONS AND SOLUTIONS |ALREADY GRADED A+ |NEWEST + |GUARANTEED PASS|LATEST UPDATE The FDA will not disclose the existence of an IDE unless: 1. FDA determines that information has been previously disclosed to public. 2. FDA approves a PMA for a device subject to an IDE or. 3. A notice of completion of a product development protocol (PDP) is in effect. What are prompt reporting guidelines? 1. Unanticipated. 2. Research places subjects or others at greater risk of harm. Examples: Deviations or changes to protocol to eliminate immediate hazards to trial subjects. Changes that increase risk to subjects or affect conduct of trial. Adverse Drug reactions (serious/related/unexpected). New info that could affect safety of subjects. What is the notification process of an exception to informed consent occurs? IRB to provide in writing to sponsor than sponsor should disclose to FDA. Determinaton of investigator to use the device must be made in 5 working days of using device to IRB. Belmont Report: Justice Who ought to receive the benefits of research and bear its burdens? "fairness in distribution" or "what is deserved". Equals ought to be treated equally. 1. To each an equal share. 2. To each according to individual need. 3. to each according to individual effort. 2 | P a g e 4. to each according to societal contribution. 5. to each according to merit. Nuremberg code 10 ethical principles set out at the end of WWII - 1947. 1. consent of human subjects is essential 2. Experiment must yield results good to society. 3. Experiment should be designed based on animal experiments that justify experiment. 4. Should avoid all unnecessary physical and mental suffering. 5. No a priori reason that death or disabling injury will occur. 6. Risk should not be greater than humanitarian importance of problem. 7. preparations/facilities proposed to protect against injury, death. 8. Only conducted by qualified people. 8. Subject can end experiment at anytime. 9. Scientist in charge must terminate experiment if needed. What is non-compliance Noncompliance with the protocol, SOPs, and GCP and/or applicable regulatory requirements by an investigator institution or by members of the sponsors staff should lead to prompt action by the sponsor to secure compliance. Required components of a Protocol (IND app/312) 1. statement of objectives/purpose. 2. Name/address/statement of qualifications of each investigator. 3. criteria for patients selection/inclusion and # of patients enrolled. 4. Description of study design. 5. method for determining dose to be administered, planned max dose and duration of exposure. 6. description of observations and measurements. 7. clinical procedures, lab tests to monitor effects of drug. Confirmation of review by IRB/IEC. The sponsor, should obtain from the investigator/institution? 1. Name/Address of investigator/institution. 2. A statement obtained from the IRB, that it is organized and operates according to GCP and the applicable laws and regulations. 3. documented IRB/IEC approval. Protocol and ICS. What two categories does the FDA place all approved IDE's? 1. Category A(Experimental): Absolute risk has not yet been established. 2. Category B (Investigational; non-experimental): Involves device types to be in classes I or II or in class III where incremental risk is the primary risk. When can the IRB use expedited review? 5 | P a g e 3. Control of investigational drug. Maintain adequate records of drug disposal, (dates, quantity, use by subjects). 4. Record Keeping. Case histories. Record retention (2 years). 5. Reporting. Progress reports. Safety Reports. PDFs. Final Reports. 6. Assurance of IRB review and compliance. Requirements for an IND exemption Clinical investigation of product marketed in US that also: 1. Is NOT to be reported to FDA in support of a new indication or support of change in labeling. 2. No significant change in advertising. 3. Does not change dose, route, patient population that significantly increases risk. 4. Drug intended for invitro or lab tests in animals. 5. Blood grouping serum/ reagent RBCs/Anti-HGB What are procedures for when ICF cannot be obtained? (E6) 1. Requires Assent when possible. 2. Normally ICF must be obtained for all non-therapeutic trials. General Requirements for ICF (CFR 46) (Basic Elements) 1. Study Involves research (People, duration, experimental parts). 2. Risk or discomforts to subject. 3. Benefits. 4. Alternative Procedures. 5. How records that identify subject will be kept confidential. 6. If research is greater then minimal risk -> compensation /treatment for injury. 7. Who to contact for questions/injury. 8. Participation is voluntary. 2.54 cm = how many inches? 1 Inch Vulnerable Subjects Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether, justified or not of benefits associated with participation or of a retaliatory response from senior members of a hierarchical structure who refuse to participate. BSA Calculation Square root of (height in cm x weight in kg) / 3600 PMA Permanent approval 1 kg equals how many pounds? 6 | P a g e 2.2 lbs What is the criteria for multicenter trials? 1. All investigators conduct the trial in strict compliance with the protocol agreed to. 2. CRFs are designed to capture the required data at all multi-sites. 3. Responsibilities of coordinating investigators are documented prior to the start of tx 4. are given instructions on following protocol, on complying with a uniform set of standards for assessment of clinical and lab findings. 5. communication between investigators is facilitated. How to go from Celsius C -> F is (F -32)/1.8. F->C is (C x 1.8) + 32 FDA 483 FDA form issued form to an institution when conditions are observed that in their judgement may constitute violations of the FDA. The form notifies the company's management of objectionable conditions. Investigator responds with in 15 days. Describes any observations that represent deviations from applicable statues and regulations. Inspector also prepares EIR -> goes to FDA with 3 outcomes: 1. No action required. 2. Voluntary Action required (response recommended generally for minor deviations). 3. Official Action indicated - major deviations) The Belmont Report Summarizes the basic principals that should underlie the conduct of biomedical and behavioral research involving human subjects. A sponsor should submit a brief report to the investigator within how many days after the IND went into effect? 60 days. Containing: 1. Individual study info. 2. Summary information. 3. Description of general investigational plan. 4. IB has been revised. 5. Significant protocol modifications. What are the 4 criteria for an SAE? 1. Death. 2. Life threatening adverse event. 7 | P a g e 3. Inpatient hospitalization or prolonged of existing hospitalization. 4. Persistent or significant incapacity to conduct normal life functions. 5. Congenital anomaly/birth defect. SAE (Definition) Any untoward medical occurrence that at any dose results in the criteria for an SAE Belmont Report: Respect for persons 1. Individuals should be treated as autonomous agents. An autonomous person is a capable individual of deliberation about personal goals. 2. Persons with diminished autonomy are entitled to protection (give weight to an autonomous person) - considered opinions and choices while refraining from obstructing their actions. IDE exempt Devices 1. No invasive sampling > minimal risk. 2. Does not introduce energy. 3. Will not be used to diagnose without another approved device or procedure. Use of placebo The benefits, risks, effectivess, etc. must be tested except: When no proven intervetion exists. Then the use of placebo, or no intervetion is acceptable. Also, if a compelling and scientific methodological reasons for intervention Public Discolsure with INDs 1. IND will not be disclosed unless previously done. 2. FDA will disclose upon request to an individual given an IND has been given copy of report on how it relates to use. Reporting Time Frames 1. Fatal or Life threatening unexpected ADRs - Qualify for rapid reporting - ASAP - no later than 7 days - follow up report no later than 8 additional days. 2. All other serious, unexpected ADRs must be filed asap - but no later than 15 calendar days. IRB will determine if study is morally justified and demonstrates what 4 key items? 1. Adequate Design. 2. Favorable Risk/Benefit ratio. 3. Equable selection of subjects. 4. ICF of subjects. Adverse Event (Definition) Any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug related. It can therefore be any unfavorable and unintended sign, symptom, or diagnosis associated with the use of a medicinal investigational product whether or not related. 10 | P a g e What is the purpose of an audit? It is independent of and separate from routine monitoring or quality control functions, should be used to evaluate trial conduct and compliance with the protocol SOP's, GCP, and the applicable regulatory requirements. Significant Risk Device IDE must be submitted. 1.Implant or serious risk to health, safety, well-being 2.Supports/sustains human life 3.Importance for diagnosis, treatment, or curing diseases. Could be class II or class III. IRB makes determination when FDA hasn't already. Criteria for IRB Approval 1. Risks to subjects are minimized 2.Risks are reasonable in relation to benefits. 3. Selection of subjects is equitable. 4.ICF is obtained from each subject or LAR. 5.ICF is appropriately documented. 6.Research plan includes monitor data collected to ensure subject safety 7.Adequate protection of privacy and confidentiality of data -> additional safeguards for vulnerable populations. How many days must the IRB revise its registration information? 90 Days What should sponsor obtain from investigator regarding IRB? 1. Name/Address of IRB 2. Statement from IRB that it is organized and complies with GCP 3. Documented approval of ICS and Protocol Record Keeping Investigators: 2 years after marketing applications approval or 2 years after investigation is discontinued and FDA is notified. Sponsor: Should maintain all sponsor specific docs for at least 2 years after they discontinue development. IRB: 3 years after completion of research. If a sponsor discontinues the clinical development of an investigational product (i.e.) for any or all indications, routes of admin, dosage forms) the sponsor should maintain all sponsor specific essential documents for at least how many years? 2 years. Can a clinical investigator submit an IDE? 11 | P a g e Yes. They can sponsor their own study. They are considered a sponsor-investigator and must comply with all responsibilities of both sponsor and investigator. IRB can use expedited reviews when? 1. Some or all of research involved no more than minimal risk. 2.Minor changes in previously reviewed research during period of 1 year or less for which approval is authorized. 3. Can be carried out by IRB chairperson or by one or more experienced reviewers. Reviewer cannot disapprove on their own. What do audits, inspections, and monitoring visits have in common? Ensure human subject protection, data integrity, and product accountability FDA jurisdiction for devices FDA has jurisdiction at international sites where investigator is under an IDE What does a Phase I study entail? 1. Initial introduction of investigational drug into humans. 2. Closely monitored 3. Patients or normal volunteers. 4. Designed to determine metabolism and pharmacologic actions of drugs in humans. 5. Side effects and increasing doses 6. Gain early evidence on effectiveness 7. drug metabolism structure activity 8. research tools. 9. 20-80 patients. Non-Significant Device IRB must agre with this risk assessment. Does not meet significant device categories. What is the IEC? Independent Ethics Committee. A review panel that is responsible for ensuring the protection of the rights, safety and well being of human subjects involved in a clinical investigation and is adequately constituted to provide asurance of that protection. An independant body ( a review board, comittee, institutional, regional, national, supre- national) constituted of medical professional and non-medical members whos responsibility it is to ensure the protection of the rights, safety, and well being of human subjects invovlved in a trial and provide public assurance of protection. What does a Phase III study entail? 1. Expanded controlled and uncontrolled studies. 2. After preliminary evidence of drug effectiveness. 3. Gather additional information (effectiveness or safety) 12 | P a g e 4. Evaluate overall benefit-risk relationship. 5. Provide adequate basis for MD labeling. 6. Several hundred to several thousands of patients. Investigational Brochure (IB) 1. A compilation of the clinical and non clinical data on the investigational product that are relevant to the study of the products in human subjects. Purpose: to provide the investigators and others involved in the trial with the info to facilitate their understanding. What is included in the IB? 1. Brief description of drug substance/formulation. 2. Pharmacological/toxicological effects in animals. 3. Package/biological disposition in animals, humans as known 4. Summary of safety/effectiveness. 5. Possible Risks/side effects FDA Inspections 1. Bioresearch monitoring program conducts. 2. Usually occurs when NDA has been submitted for marketing approval. 3. Involve interviewers with research personel, review of reg. records, data, FDA/GCP guidelines. Study Oriented: Review of data that supports NDA, PMA, bioequivilance. Investigator Oriented: usually due to complaints, misconduct, fraud What would initiate the need for a protocol amendment? 1. znre protocol 2. Changes in protocol 3. New investigator 4. Content and format The sponsor must notify the FDA and investigators of potential serious risks ASAP - But no later than how many days? 15 calendar days (After sponsor determins info qualifies for reporting) Descirbe the membership and reporting requrements of IRBs? 1. 5 members with varying backgrounds. 2. Mix of gender and professions. 3. Include at least (1) primary concern is scientific (1) whose primary concern is non-science 4. Include at least (1)not affiliated with institution or immediate family. 5. No member participation in initial or CR of any project in which there is conflict of interest. 6. At discretion they can invite people with competence in special areas for complex issues. Investigator Commitments on 1572 (CFR 312) 15 | P a g e 1. Name, address, institution, contact info of head official. 2. Contact info for who is doing registration. 3. Contact info for chairperson. 4. # of protocols, active protocols, # of IRB positions. 5. Type of products for protocols they review. OHRP approves registration- effective for 3 years. Additional Elements of ICF that should be provded (CFR 46) 1. Treatment may involve risks which are currently unforeseeable. 2. Subject protection may be terminated by investigator. 3. Additional costs that may result from participation. 4. Consequences of withdrawing or termination. 5. New findings will be provided when they may offset willingness to participate. 6. Number of subjects involved. Expanded Access to Investigational Drugs Requirements Meant to facility availability of drugs to patients with serious diagnosis or conditions and there is not alternative. Drugs with limited availability by REMS. 1. Patients have serious or immediately life threatening condition with no alternatives. 2. Benefit justifies risk of treatment use and potential risks are not unreasonable. 3. Providing the drug for use will not interfere with clinical investigations or compromise potential development. 4. Expanded access submission submitted. Goes into effect 30 days after FDA reviews. What are the IRBs responsibilities when ICF cannot be obtained in emergency situations Must ensure procedures are in place to inform at earliest time the subject or LAR of the subjects participation in the study. IRB determinations of this must be retained for 3 yrs. Must document: Life treatening. ICF is not feasible. Research will cause direct benefit. Waiver not practical. What are the contents of an IND application? 1. 1571. Name of sponsor, phase of study, will wait for IND approval, IRB responsible, Name of people monitoring, who is evaluating safety, statement of any transferred responsibilities, signature. 2. Table of contents. 3. Intro statement. 4. IB. 5. Protocol. 6. Chemistry, manufacturing, control info. 7. Pharmacology, toxicology info. Declaration of Helsinki (1964) Ethical principles for medical research addressed primarily to physicians 1. Health of patient is 1st consideration. 2. Duty of physicians to provide and safeguard health and well being. 3. Number 1 purpose of research is to understand causes, development, effect of disease and improve 16 | P a g e prevention, diagnoses and interventions. 4. new research knowledge is never greater rights of interests of subjects. 5. Duty of physicians to protect health, life, dignity, integrity, privacy and confidentiality. 6. Research should be done so as to minimize possible harm. What are the 8 basic elements of the informed consent? 1. A statement that study involves research explanation of procedures, purpose, participation. 2. A description of risks. 3. A description of benefits. 4. A description of alternative procedures/treatments. 5. Confidentiality. 6. If involves more that minimal risk - medical treatment/compensation involved. 7. Study contact questions. 8. Participation is voluntary. What are information amendments (312, IND) A sponsor must report information on the IND that is not within scope of protocol amendment. Ex: 1. Toxicology, chemistry technical info. 2. Report for discontinuation of investigation. What should a protocol contain? 1. Objectives and purpose of study. 2. Investigators information - address, name, etc. 3. Criteria for pt. selection and # of pts. 4. Description of study design. 5. Method of determining dosage - max dose/duration. 6. Observations and measurements. 7. Description of clinical procedures. Responsibilities of sponsors ( CFR pt 312) 1. Select Qualified Investigators 2. Provide investigator with info they need to conduct trial. 3. Proper monitoring. 4. Maintain IND (amendment/renewals). 5. Notify FDA and all investigators of significant AEs or updated risk information of drug. 6. Protocol/investigational plan is followed. (Some of these can be transferred to the CRO) How long does the sponsor have to notify the FDA about a protocol amendment for an investigator change? 30 days 17 | P a g e Protocol Amendments (sponsor can amend as needed the protocol to ensure investigations are conducted according to protocol in application) A sponsor shall submit an amendment when there is any change that affects patient safety. 1. Increase in drug dosage or exposure. 2. Increase in number of subjects in study. 3. Addition of any new test or procedure (must submit to FDA and must be IRB approved). 4. Change in design of protocol. If change in protocol has to be done immediately to protect subjects they can be notified ASAP. New investigator -> sponsor must notify FDA within 30 days. Humanitarian Use Device 1. Treatment of diagnosis in condition affecting fewer than 4000. 2. FDA responds in 45 days. 3. HDE not equal to IDE. Only needs to address safety. The sponsor should obtain the investigators agreement for a new trial based on what 4 criteria? 1. To conduct the trial in compliance with GCP, with the applicable reg requirements, and with the protocol agreed to by the sponsor. 2. to comply with procedures for data recording/reporting. 3. to permit monitoring, auditing, and inspection. 4. to retain trial related essential documents until sponsor informs investigator these are no longer needed. 2 common routes for a device to go to market 1. Premarket notification (SIO). FDA determines device is equivalent to device already allowed on market. Can enter market without clinical trials. 2. Pre-market approval (PMA) - similar to NDA. FDA reviews all clinical investigations. What is the sponsor responsible for in terms of electronic data systems? 1. Ensure and document electronic system is complete, accurate, and consistent. 2. Maintain SOPs for system. 3. Data changes are documented, no deletion of data. 4. List of authorized individuals. Expanded Use Criteria 1. Patient has life threatening diagnosis or condition. 2. Benefit outweighs risks. 3. Providing investigational drug for requested use. 1571 = IND Application (Expanded Use) Cover sheet for expanded access submissions includes: 1. Rationale of intended use of drug. 20 | P a g e Employ at least 2 identification components - such as an identification code AND a password. Name some CONTROLS for the identification components (i.e. identification code and password) for e- signature? 1. no 2 people should have the same identification controls (password... code) 2. Identification codes and passwords should be periodically checked, revised, etc. 3. Deauthorize lost, stolen, missing codes and passwords 4. Periodically test your devices that generate these codes Can an informed consent contain exculpatory language? NO! Cannot say things like "you are waiving your right to damages" etc When may an experimental drug or device be used on a patient WITHOUT informed consent? ((EMERGENCY USE)) 1. the investigator and an independent physician agree that the patient is -life threatening situation -informed consent cannot be obtained - there is no time to obtain consent from th esubject's legal representation -there is no recognized therapy that provides equal or greater likelihood of saving life - within 5 working days this must be evaluated by another independent physician -documentation must be submitted to the IRB within 5 working days -the president can authorize use on the military (lots of information on this military stuff..) When is it okay to skip informed consent and perform ((EMERGENCY RESEARCH))? 1. Human subjects are in life threatening danger, available treatments are unproven or unsatisfactory, and collection of valid science is needed 2. Obtaining consent is not feasible -subjects can't consent due to medical state -can't feasibly get LAR consent in time -no reasonable way to identify ahead of time individuals who will be eligible for participation 3. Participation holds the prospect of direct benefit to subjects -animal/preclinical studies support it -risks are reasonable 4. could not practicably be carried out without waiver of consent 5. OTHER protective measures are in place (counseling, disclosure, disclosure to public, data monitoring committee ETC Name the 8 elements of INFORMED CONSENT 1. statement of research. purpose of research. duration of participation. procedures involved. identification of all that is experimental. 2. Risks and discomforts 3. Benefits 4. Disclosure of alternatives 5. Confidentiality 6. Compensation if injury 21 | P a g e 7. Who to contact 8. Statement of voluntariness ADDITIONAL: Costs, pregnancy, termination of participation, withdrawal consequences, disclosure of findings, number of subjects in the study. Clinicaltrials.gov statement. Short Form consent In the context of human subjects research, a written document stating that the elements of informed consent required by the Common Rule have been ORALLY presented to and understood by the subject or the subject's legally authorized representative When can children participate in clinical trials ? (conditions) 1. No more than minimal risk 2. Adequate assent of the child 3. Risk is justified by potential benefit 4. Risk is above minimal, but likely to yield knowledge about a disorder or condition. Not reasonably different from their expected medical course. Assent. Things to consider when soliciting ASSENT Age, maturity, mental capacity When is ASSENT NOT REQUIRED? Children cannot be reasonably consulted in this case. Benefit is so great. Minimal risk. Could not practicably be carried out without the waiver. When can WARDS be included? related to their status as wards, conducted in a setting (school) where most are not wards, advocate has experience to act in the best interest of the child (cannot be associated with study team) Within how many days can emergency use of a test article be reported to the IRB? 5 Do IRBs need to register with the federal government? Yes! Every IRB that reviews clinical investigations must register under HHS How many members are required to be on an IRB? 5 members, with varying backgrounds to promote complete and adequate review of researchj Do the members of an IRB have to represent adequate diversity of backgrounds, race, vulnerability? Yes Each IRB shall include atleast 1 _________ and atleast one _______ (3 categories) 22 | P a g e Scientific member and non scientific member. Institution affiliated and NON institution affiliated Man and Woman Do a majority of IRB members need to be present when reviewing protocols? I think so. And you definitely need one nonscientific person. Does an IRB have to write out its reasons for not approving an IRB? Yes. It must allow the investigators appropriate response. Does an IRB have to do a yearly continuing review? Review of research at intervals appropriate to the degree of risk, not less than once per year (I suppose this could mean modifications like CHOP) When can an IRB use an expedited review method? Research is no more than minimal risk OR minor changes to previously approved research What criteria must be met for an IRB to approve a study? -Risks are MINIMIZED -Risks are reasonable in proportion to benefits -Selection of subjects is equitable -Informed consent will be sought -Informed consent will be appropriately documented -Data will be monitored for subject safety -Adequate provisions to protect privacy and confidentiality -Additional safeguards are in place for vulnerable subjects -All research is in complianace with FDA part 50, subpart D Can an IRB suspend or terminate research? Yes. If unanticipated harm, or if researchers are not following IRB requirements How long are IRB records required to be maintained after completion of a study? 3 years (and accessible!). FDA can shut it down if IRBs are not keeping records appropriately Are there a lot of required documentations and records by the IRB? Yes. Lots of written procedures, must keep copies of meeting minutes, copies of correspondance, research proposals etc. Everything needs to be documented! Does the FDA have the power to shut down, stop studies, etc if an IRB is not operating in compliance? Yes! Can full on disqualify if they repeatedly dont comply. When does a research drug need an IND? 25 | P a g e Uphold their investigator's agreement and conduct study according to plan. Obtain informed consent. What type of records to investigators need to keep, and for how long after marketing approval? Disposition of drug records, case histories. For 2 years. Who submits annual reports to FDA, the investigator or the sponsor? The sponsor. Who submits reports of SAEs, and to whom? The investigators report to the sponsor, and also to the IRB i think Can a clinical investigator be disqualified? Why might that be the case? Yes - if repeatedly or deliberately failed to comply with subparts, agreements etc, or falsified any information. Is there a different set of regulations when it comes to life-threatening / debilitating diseases for which no good alternatives exist? Yes, evaluate the risk-benefit ratio differently Can drugs be imported and exported for clinical trials? Yes, under specified circumstances and with proper review etc. Can the FDA "rely" on an "external" FDA in a multi-national trial? Yes - you can accept foreign IND's if they were conducted under GCP etc, if the FDA can validate the data, and also need to submit lots of regulatory stuff. Is an IND application automatically public knowledge? No, it can be if investigator's want it to be. expanded access The use of an investigational new drug (IND) outside of a clinical trial by patients with serious or life- threatening conditions who do not meet the enrollment criteria for the clinical trial in progress. Requires an application. Can a special access be granted for small patient populations, i.e. orphan drugs, orphan conditions? Yes - special considerations. Do the policies of devices largely mirror the policies for investigational new drugs? Yes, mirrored closely Federal Regulations Part 45/46 Protection of Human Subjects - Protection of Public Welfare 26 | P a g e Federal Regulations Part 21 Electronic Records, Human Subjects (50), IRB, IND, Investigational Devices 04955D auth code smh What types ofhuman subjects research could be considered exempt from human subjects review/regulation? Schools, educational tests, unidentifiable subjects, benign behavioral interventions, secondary research, public services research, expedited review a review of study proposals that pose minimal risk to subjects; one or two IRB members participate What are requirements for waiver of informed consent? Minimal risk, and could not be practicably be carried out without the waiver When may fetuses or pregnant women be included in research? -pregnant animals and non pregnant people have already been assessed for risk -risk to fetus/pregnant women is less than direct benefit -there is minimal risk to woman and fetus -this biological knowledge can be obtained by no other means If benefit is EXCLUSIVE to the fetus, with no benefit to the pregnant woman, who needs to consent? woman and father (there are exceptions for rape, artificial insemination, death/disability, and unavailability) If there is no risk/benefit for the fetus, only a potential risk/benefit for mom, who needs to consent? pregnant woman only Are there protections for coerced abortion for research? Yes. You cannot compensate for a terminated pregnancy.The individuals doing the research cannot determine the viability of pregnancies or timing of terminations. When can nonviable and questionably viable neonates be included in research? preclinical/clinical studies have been conducted. -researchers have no role in determining viability -research enhances possibility of survival -biomedical knowledge cannot be obtained ANY other way If Nonviable neonates are included in research... what are some protections that limit the research that can be done on them? 27 | P a g e Cannot artificially maintain a heartbeat or vitals -cannot TERMINATE the heartbeat or respiration/ vitals -No additional risk to the neonate -biomedical knowledge cannot be obtained any other way For a nonviable neonate, who needs to consent? Both parents (exceptions for unavailability, rape, incest etc) IRB rules when prison research is involved majority of the IRB members can have no relation to the prisoners. A prisoner or prisoner representative with appropriate background must serve Name some protections against coercion in prison research Cannot affect his/her parole status. Cannot give advantages or compensation that would coerce. Subject selection must be equitable/random. When can research include prisoners? If it is RELEVANT to incarcerated peoples. Does the FDA define the term children in terms of years? No. A child is someone who cannot legally consent to treatments or procedures in research (defined locally) Describe some instances when children MAY be included in research. -Minimal risk -risk is small in comparison to direct anticipated benefit -NO OTHER WAY of obtaining this information -appropriate preclinical trials -yield knowledge about a disease or condition -adequate assent/consent in place When is assent not needed? -Children are incapacitated/not sound to assent -Benefit is so great to the child -minimal risk Are there instances in which both parents need to consent for a child to participate in research? YES. I suppose more than minimal risk? of course, there are exceptions Are there exceptions for parental consent when a child is neglected or abused? Yes When can WARDS be included in research? 30 | P a g e Research: an activity to test a hypothesis, develop generalizable knowledge. Formal protocol and procedures defined. respect for persons treating persons as autonomous agents and protecting those with diminished autonomy (relates to children, prisoners, mental disability, respect for peoples opinions and judgements) Beneficence (Definition) Maximize possible benefits and minimize possible harms. Belmont Report: Justice fair balance between those who participate and those who benefit. (good distribution of BURDENS vs. Benefits) you can't study prisoners to benefit larger society (and other examples) What are the 3 important elements of informed consent, as outlined in the Belmont Report applications? Information, Comprehension, Voluntariness Describe the differences in information, comprehension, voluntariness Information is WHAT is presented. Comprehension is HOW it is presented (time, organization, layman's terms, simple english). Voluntariness is freedom from coercion and influence (like from powerful people/power imbalance/threats) How should selection of subjects be systematically approached? Adults before children, capable before incapable, free before unfree etc. Free from social, racial cultural biases. Why is the Nuremburg Code such named? Came about from the trials held in Nuremburg Germany to prosecute unethical human experimentation in concentration camps Describe (in brief) the 10 principles set forth by the Nuremburg Code 1. Voluntary Consent of the subject 2. Fruitful results unprocurable by other methods 3. Based on animal results and natural history 4. Avoid ALL unnecessary suffering 5. Cannot conduct study in which death or disability will reasonably occur 6. Degree of risk should NEVER outweigh societal benefit 7. Proper preparations and adequate facilities to protect subjects 8. Only conducted by scientifically qualified persons with the highest skill and care 9. Human subjects must be at liberty to bring the experimentation on them to an end 31 | P a g e 10. Investigator must terminate any experiment when he has probably cause to believe death, injury, or disability is likely Please order dec of helsinki, belmont report, and nuremburg code in chronological order 1. Nuremburg code (40s) 2. Dec of Helsinki (60s) 3. Belmont report (70s) Who is the target audience of the Declaration of Helsinki? Physicians Loosely describe the contents of the declaration of helsinki Contains a lot of information that the other reports have. Principles of consent, investigator qualification, use of placebo, post-trial provisions, honestly kind of all over the place. Protection of vulnerable subjects, etc. Contrast an adverse drug reaction with an adverse event AEs don't have to be related to the drug/intervention. For ADRs, there is some possibility they are related. Please name the 9 sections of the ICH GCP 1. Definitions 2. 10 original Principles of GCP 3. IRB 4. Investigator 5. Sponsor 6. Protocol 7. Investigator's Brochure 8. Essential Documents for clinical trials 9. Paperwork Reduction Act Please name the 10 Principles of GCP (can include amendments) 1. Conducted according to Dec of Helsinki ethics 2. Risks must be in proportion to benefit 3. Wellbeing of individual subjects is more important than anything 4. Information (clin and non-clin) on an investigational product must be thorough 5. Scientifically sound protocol 6. Approved by IRB 7. Investigators must be QUALIFIED 8. Every individual involved in a trial must be QUALIFIED 9. CONSENT 10. Accurate reporting, interpretation, and verification of data are crucial 11. Confidentiality protected 32 | P a g e 12. Good Manufacturing Practice for drugs/devices 13. SYSTEMS in place to assure quality and safety Is the IRB responsible for reviewing investigator qualifications? Apparently, yes. Along with research procedures. Are prorated compensation models more ethical than entire completion models? Yes! Good to know! Can't unduly coerce them to remain in the study Name 4 categories of EVENTS that require submission to the IRB 1. Protocol Deviations or Changes 2. Changes that increase risk 3. all Adverse Drug Reactions that are SERIOUS and UNEXPECTED 4. New information that may affect subjects/trial Does an investigator need to show that have the resources - money, time, staff, qualifications, power to complete their trial Yes Are participants obliged to give a reason when withdrawing from a trial? No, but if possible they should To whom would you report a protocol deviation, as an investigator? IRB and SPONSOR. If required, to regulatory authorities How does one consent if they can't read? Oral explanation with a signature from an IMPArTIAL WITNESS How does a non-therapeutic trial differ from a therapeutic trial? There is no anticipated benefit for the subject. This makes it less appealing to participate. It should be an autonomous person's decision to participate in a non-therapeutic trial. Whenever possible, LARs should not enroll their dependents in such trials because there is no expected benefit. (THERE ARE EXPECTATIONS) Changes to SOURCE DATA must be.... TRACEABLE!!! (electronic audits or handwritten single strikethorugh with date and initials!) Should SAEs be reported to the sponsor? Yes. Immediately. Can follow up later with a detailed report IF a trial is ended prematurely, are you supposed to tell prior participants? Yes allocation of responsibility 35 | P a g e knowledge of the natural history of the disease. 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. 5. No experiment should be conducted where there is an a prior reason to believe that death or disabling injury will occur. 6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. 7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. 8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care. 9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end. 10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage. Nuremberg Code - Key Principles 1. Voluntary participation 2. Informed Consent 3. Minimization of risk The Nuremberg Code and the Declaration of Helsinki are the basis for the... Code of Federal Regulations Title 45 Volume 46 which are regulations issued by the United states department of heath and human services Declaration of Helsinki (1964) Is a set of ethical principles regarding human experimentation developed for the medical community by the WMA (World Medical Association). Declaration is addressed primarily to physicians. The WMA (World Medical Association) encourages others who are involved in medical research involving human subjects to adopt these principles. Not legally mandated Declaration of Helsinki Key Principles 1. Well-being of subjects takes precedence 2. Respect for persons 3. Protection of subjects heath and rights 5. Special protection for vulnerable populations Declaration of Helsinki has undergone.. 7 revisions and 2 clarifications - first in Finland in June 1964 Who developed the Declaration of Helsinki and why 36 | P a g e The World Medical Associated (WMA) - as a statement of ethical principals for medical research involving human subjects, including research on identifiable human material and data General Principals of the Declaration of Helsinki 1. "the health of my patient will be my first consideration" 2. It is the duty of the clinician to promote and safeguard the health, well-being and rights of patients 3. Medical progress is based on research that ultimately must include studies involving human subjects 4. The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases 5. Medical research is subject to ethical standards that promote and ensure respect for all human subjects and protect their heath and rights 6. While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects 7. It is the duty of clinicians who are involved in medical research to protect the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects 8. Physicians must consider the ethical, legal and regulatory norms and standards for research involving human subjects in their own countries as well as applicable international norms and standards 9. Medical research must be conducted in a manner that minimizes possible harm to the environment 10. Medical research involving human subjects must be conducted only by individuals with the appropriate ethics and and scientific education, training and qualifications 11. Groups that are underrepresented in medical research should be provided appropriate access to participation in research 12. Physicians who combine medical research with medical care should involve their patients in research only to the extent that is justified by its potential preventative, diagnostic or therapeutic value 13. Appropriate compensation and treatment for subjects who are harmed as a result of participating in research must be ensured The Belmont Report April 18th, 1979 1. Respect for persons-informed consent, protection of vulnerable populations 2. Beneficence-non malfeasance 3. Justice-fairness These principles remain the basis for the United States Department of Health and Human Services (HSS) Human Subject Protection regulations The Belmont report was created/established by... The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1979 Prompted from the Tuskegee-Syphilis Study (1932-1972) Tuskegee Syphilis Study 37 | P a g e (1932-1972) prompted the belmont report Conducted by the US Public Heath Service to study the natural progression of untreated syphilis in rural African american men who thought they were receiving free healthcare from the US government In 1947 the treatment for syphilis (penicillin) had become standard trx - the experiment continued The Belmont Report continues as an essential reference for IRB 1. They must make sure the study is approved by an IRB 2. Get Informed consent from the patient 3. Be sure that the patient understands the full extent to the experiment, and if not contact the study coordinator 4. Make sure the patient wasnt coerced into doing the experiment by means of threatening or bullying 5. Be careful of other effects of the clinical trial that was not mentioned and report it to the proper study coordinator 6. Support the privacy of the patients identity, their motivation to join or refuse the experiment. 7. Ensure all patients get at the least, minimum care needed July 12, 1974 The national research act was signed into law - creating the national commission for the protection of human subjects of biomedical and behavioral research Today the Belmont Report Serves.. As a historical document and provides the moral framework for understanding regulations in the US on the uses of humans in experimental research Ethical Principals and Guidelines for Research Involving Human Subjects Belmont Report A. Boundaries Between Practice and Research B. Basic Ethical Principles 1. Respect for Persons 2. Beneficence 3. Justice C. Applications 1. Informed Consent 2. Assessment of Risk and Benefits 3. Selection of Subjects Boundaries Between Practice and Reasearch Research and practice may be carried on together when research is designed to evaluate the safety and efficacy of a therapy. This need not cause any confusion regarding whether or not the activity requires review; the general rule is that if there is any element of research in an activity, that activity should undergo review for the protection of human subjects. 40 | P a g e -Prior to trial initiation, submit any required applications to the appropriate authorities for review, acceptance, and or permission -Ensure timely delivery of the investigation products to the investigators -maintain records that document shipment, receipt, dispositions, return and destruction of the investigational products -maintain a system for retrieving investigational products and documenting this retrieval -Maintain a system for the disposition of unused investigational products and for the documentation of this disposition -Take steps to ensure the investigational products are stable over the period of use -maintain sufficient quantities of the investigational product use in the trials to reconfirm speculations -promptly notify all concerned investigators/institutions and the regualatory authorities of findings that could affect the adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's approval/favorable option to continue the trial -Expedite the reporting to all concerned investigators/institutions to the IRB/IEC, where required and to the regulatory authorities of all adverse drug reactions (ADR's) that are both serious and unexpected -Ensure trials are adequately MONITORED -Determine the approximate extent and nature of monitoring -Statistically controlled sampling may be acceptable method for selecting the data to be verified The sponsor should... When using electronic trial data handling and/or remote electronic trial data systems: -ensure and document that the electronic data system conforms to the sponsors established requirements for completeness, accuracy, reliability and consistent intended performance -Maintains SOP's for using these systems -Ensures that the systems are designed to permit data changes in such a way that data changes are documented and that there is no deletion of entered data -Maintain a security system that prevents unauthorized access to the data -Maintain a list of individuals who are authorized to make data changes -Maintain adequate backup of the data -Safeguard the blinding (maintain the blinding during DE and processing) What are the three main basic ethical principles of the Belmont Report? 1.Respect for Persons 2. Beneficence 3. Justice What are the applications for the Belmont Report? 1. Informed Consent 2. Assessment of Risk and Benefits 3. Selection of Subjects The "Doctor's Trial" prompted the Belmont Report T/F False - The tuskegee syphilis study 41 | P a g e The objective of the ICH GCP Guideline is to provide a unified standard for the European Union (EU, Japan and the Untied States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions T/F True The World Medical Association (WMA) ethical principals for medical research involving human subjects is called? The Declaration of Helsinki The object of GCP is part of the ICH mission statement T/F True What is HHS? Department of Health and Human Services The international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects is known as Good Clinical Practice (GCP) Purpose of trial monitoring -the rights and well being of human subjects are protected -the reported trial data are accurate, complete and verifiable from source documents -The conduct of the trial is in compliance with the currently approved protocol/amendments, with GCP and with the applicable regulatroy requirements Monitoring plan considerations -trial objectives, design, endpoints -trial complexity -number/location of investigators -type of investigational product -disease under study -written monitoring/auditing SOP's Components of a monitoring visit -pre-investigation -study initiation -periodic -final close-out Monitoring report -Monitor should submit a written report to the sponsor after each site visit or site communication -Reports should include the date, site, name of the monitor, name of the investigator or other individuals contacted 42 | P a g e -Reports should include a summary of what was reviewed, the monitors statements concerning the significant findings/facts, deviations/deficiencies, conclusions, actions taken or to be taken, and/or actions recommended to ensure compliance Monitor follow-up -Send letter and document findings and recommend solutions -Confirm next visit -Complete monitoring report -transmit CRF's -Update flowsheet Frequency of monitoring Visits should be frequent enough to ensure: -Facilities used by the investigator continue to be acceptable for purposes of study -study protocol or investigational plan is being followed -changes to protocol have been approved by the IRB and or reported to sponsor and IRB -accurate, complete, and current records are maintained -accurate, complete and timely reports are made to the sponsor and IRB -investigator is carrying out the agreed upon activities and has no delegated them to unspecified staff Sponsors Responsibilities - Non compliance -Non compliance with the protocol, SOPs, GCP and or applicable regulatory requirements by an investigator/institution or by members of the sponsors staff should lead to prompt action by the sponsor to secure compliance -If monitoring/auditing identifies serious and/or persistent noncomplicance on the part of an investigator/institution, the sponsor should terminate the investigator/institutions participation in the trial -when an investigators institution participation is terminated because of noncompliance, the sponsor should notify promptly the regulatory authorities What best describes the goals of an investigators meeting Review the protocol and CRF with the clinical site personnel Investigators have the choice to decide on which of the following during the course of a trial A. Monitoring B. Auditing C. Follow GCP's D. Terminate a subjects participation in the best interest of the subject C. Follow GCP's LAR can sign for subjects in a non-therapeutic trial without any exception T/F False 45 | P a g e An independent data monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. Monitoring Report A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs SOPs (standard operating procedures) Detailed, written instructions to achieve uniformity of the performance of a specific function Quality Assurance (QA) All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented, and reported in compliance with Good Clinical Practices and the applicable regulatory requirements. (ICH GCP E6 1.46) -Ensures quality in the PROCESS: by which products are developed (to ensure defects do not arise when the product is being developed) Quality Control (QC) The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled. (ICH GCP E6 1.47) -Ensures quality in the PRODUCTS: by identifying defects in the actual products produced (after a product is developed, before it is released) Sponsor-Investigator An individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any other person other than an individual, e.g. corporation or agency. (21 CFR, sec. 50.3) -The obligations of a sponsor-investigator include both those of a sponsor and investigator The principles of ICH-GCP -Clinical trials should be conducted in accordance with the ethical principles that have their origin in the deceleration of helenski -A trial should be initiated only if the anticipated benefits justify the risks -the rights, safety and well-being of the trial subjects are most important considerations and should prevail over interests of science or society -the available nonclinical and clinical information on an investigational product should be adequate to support the proposed clinical trial -clinical trials should be scientifically sound, and described in a clear, detailed protocol - a trial should be conducted in compliance with protocol that has received prior institutional review board (IRB) / independent ethics comitte (IEC) approval / favorable option -the medical care given, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate of a qualified dentist 46 | P a g e -each individual involved in conducting a trial should be qualified by education, training and experience to perform their respective tasks -freely given informed consent should be obtained from every subject prior to clinical trial preparation -all clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification -the confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements -investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol -systems with procedures that assure the quality of every aspect of the trial should be implemented An IRB/IEC should... -Safeguard the rights, safety, and well-being of all clinical trial subjects (special attention should be paid to trials that may include vulnerable subjects) -obtain documents -conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human subjects, but at LEAST once per year -Review both the amount and method of payment to subjects to assure that neither presents problems of coercion or undue influence on the trial subjects An IRB/IEC should obtain the following documents -trial procedures/amendments -written informed consent and updates -procedures (advertisements) -written information to be provided to subjects -investigators brochure (IB), available safety information -information about payments and compensation available to subjects -investigators current curriculum vitae and/or other documentation evidencing qualifications -any other documents that the IRB/IEC may require to fulfill its responsibilities An IRB/IEC should review a proposed clinical trial within a reasonable time and document is views in writing, clearly identifying the trial, the documents reviewed, and the dates for the following: -approval/favorable opinion -modifications require prior to its approval/favorable option -disapproval/negative opinion -termination/suspension o any prior approval/favorable opinion An IRB/IEC should determine that the proposed protocol and/or other documents adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials in the following circumstances: -When a nontheraputic trial is to be carried out with the consent of the subjects LAR -Where the protocol indicates that prior consent of the trial subject or the subjects LAR is not possible(in emergency situations) 47 | P a g e It is recommended that the IRB/IEC should include -At least 5 members -At least ONE member whose primary area of interest is in a nonscientific area -at least one member who is independent of the institution/trial site Who can vote/provide opinion on a trial related matter Only those members who are independent of the investigator and the sponsor of the trial The IRB/IEC should establish, document in writing and follow the procedures, which should include: -determining its composition (names and qualifications of members) and authority under which it is established -scheduling, notifying its members and conducting its meetings -conducting initial and CR of trials -determining the frequency of CR as appropriate -providing, according to the applicable regulatory requirements, expedited review and approval/favorable opinion of minor changes in ongoing trials that have the approval/favorable opinion of the IRB/IEC -specifying that no deviations from, or changes of the protocol should be initiated without prior written IRB/IEC approval/favorable opinion of an appropriate amendment, except when necessary to eliminate hazards to the subjects or when the change involves only logistial or administrative aspects of the trial (change of monitors, telephone numbers, etc) -specifying that the investigator should promptly report to the IRC/IEC -specifying that the IRB/IEC promptly notify in writing the investigator/institution The investigator should REPORT promptly to the IRB/IEC when: -Deviations from, or changes of the protocol to eliminate immediate hazards to the trial subjects -Changes increasing the risk to subjects and/or affecting significantly the conduct of the trial -All adverse drug reactions (ADR) that are both serious and unexpected -New information that may affect adversely the safety of the subjects or the conduct of the trial The IRB/IEC promptly notify in WRITING the investigator/institution concerning: -Its trial related decisions/opinions -The reasons for its decisions/opinions -Procedures for appeal of its decisions/opinions Quality assurance (QA) assures quality in the___ Processes Quality Control (QC) assures quality in the ___ Products A trial should be initiated only if the anticipated benefits justify the risks T/F True 50 | P a g e illnesses -the type and duration of follow-up for subjects after adverse events 6.9 Statistics -a description of the statistical methods to be employed, including timing of any planned interim analysis -the number of subjects planned to be enrolled. In multicenter trials, the number of enrolled subjects protected for each trial sites should be specified. reason for choice of sample size, including reflections on the power of the trial and clinician justification -the level of significance to be used -criteria for the termination for the trial -procedure for accounting for missing, unused, and spurious data -procedures for reporting aby deviations from the original statistical plan (any deviations from the original statistical plan should be described and justified in the protocol and or in the final report as appropriate). -the selection of subjects to be included in the analyses (all randomized subjects, all dosed subjects, all eligible subjects). 6/10 Direct Access to Source Data/Documents -the sponsor should ensure that it is specified in the protocol or other written agreement that the investigators/institutions will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspections by providing direct access to source data/documents 6.11-6.13 -6.11 Quality control and assurance -6.12 Ethics: description of ethical considerations relating to the trial -6.13 Data handling and recordkeeping 6.14-6.16 -6.14 Financing and insurance: financing and insurance if not addressed in a separate agreement -6.15 Publication policy: publication policy, if not addressed in sperate document 6.16 Supplements * Since the protocol and clinical trial/study report are closely related, further relevant information can be found in the ICH guidance for structure and content of clinical study reports 7.1 Introduction (IB) -The investigators brochure (IB) is a complication of the clinical and nonclinical data on the relevant investigational products in human subjects -Its purpose is to provide the investigators and others involved in the trial with the information to facilitate understanding, rationale, and compliance with key features in the protocol -It also provides insight to support the clinical management o the study subjects during the trial -The information should be presented in concise, simple objective, balanced and nonpromotional form that enables the clinician, or potential investigator to understand it and to make an unbiased risk- benefit assessment of the trial 51 | P a g e -the IB should be reviewed at least ANNUALY and revised as necessary in complicate with the sponsors written procedures. More frequent revision may be appropriate depending on the stage of development and the generation of relevant new information -However, in accordance with GCP, relevant new information may be important enough that it should be communicated to the investigators, IRB, IEC ad or regulatory authorities before it is included in a revised IB. -Generally, the SPONSOR is responsible for ensuring that an up-to date IB is made available to the investigators and the INVESTIGATORS are responsible for providing the up-to date IB to the responsible IRBs/IECs -If the investigational product is provided by the sponsor-investigator then he or she should provide the necessary information to the trial personnel - as a substitute an expanded background information section in the trial protocol that contains the minimum current information described in this guidance 7.2 General Considerations (IB) -Title page: sponsors name, identify each investigational product, research number, chemical/approved generic name and trade names where legally permissible by the sponsor -confidentiality statement: the sponsor may wish to include a statement instructing the investigator/recipients to treat the IB as a confidential document for the sole information and use of the investigators team and the IRB/IEC 7.3 Contents of the IB -table of contents -summary: a prief summary (not exceeding 2 pages) should be given, highlighting the significant physical and chemical aspects, and any clinical information available that is relevant to the stage of clinical development of the investigational product -introduction: brief introductory statement should be provided that contains the chemical name of investigational product, the active ingredients, the investigational products pharmacological class and its expected position within this class, the rational for performing research, the anticipated prophylactic, therapeutic or diagnostic indications, the general approach to be followed in evaluation the investigational product -physical, chemical and pharmaceutical properties and formulation -Nonclincial studies: results of all nonrelevant studies should be provided. Should discuss methology used, results and discussion of relevance of findings to the investigational product and possible favorable and unintended effects in humans, species tested, number/sex tested, unit does, administration route, information and results of follow-up -Effects in humans: throughout discussion of the known effects of the investigational product in humans 7.1 Appendix 1 Example of title page -Sponsor name -Product -Research number -Names (chemical, generic, trade names) -Edition number 52 | P a g e -Release date -Replaces previous edition number -Date 7.2 Appendix 2 Example of Table of Contents -Confidentiality statement (if applicable) -Signature page (optional) -Table of contents -Summary -Introduction -Physical, chemical and pharmaceutical properties and formulation -non clinical studies (nonclinical pharmacology, pharmacokinetics and product metabolism in animals, toxicology) -Effects in humans (pharmacokinetics and product metabolism in humans, safety and efficacy, marketing expertise) -Summary of data and guidance for investigator(publications, reports) -Appendices if any Essential Documents for the Conduct of a Clinical Trial 8.1 Introduction -essential documents are those documents that individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced, to serve and demonstrate the compliance of the investigator, sponsor and monitor with standards of GCP and all applicable regulatory requirements -filing essential documents at the investigator/institution and sponsor sites can greatly assist in the successful management of the trial by the investigator, monitor and sponsor -essential document's are usually audited by the sponsors independent audit function and inspected by the regulatory authorities as part of the process to confirm the validly of the trial conduct and integrality of the data collected 8.2 Before the Clinical Phase of the Trial Commences -Investigators brochure (IB) -Signed protocol and amendments (if any) and sample case report form (CRF) -Information given to trial subject (informed consent, etc) -Financial aspects of the trial -Insurance statement (where required) -signed agreement between involved parties (investigator/institution and sponsor, investigator/institution and CRO, sponsor and CRO) -dated and documented approval/favorable opinion of IRB/IEC of the following (protocol/amendments, CRF, informed consent forms, etc) -IRB and IEC composition -regulatory authority authorization/approval/notification of protocol -curriculum viate and or other relevant documents evidencing qualifications of investigators and sub investigators