SOCRA 2

The packaging of investigational drugs should ideally - Look like a marketed product - Be attractive so the study coordinators will use it - Be designed to help with subject compliance - Allow subjects to identify placebo pills

Be designed to help with subject compliance

Adverse Reaction

DIRECT relationship between event and product

before an investigational product can be shipped to an investigator, the research sponsor must file

Form FDA 1571, Investigational New Drug (IND) with the FDA

Who has ultimate responsibility for an investigational product at the study site? - Pharmacist - Study subject - Qualified/Principal Investigator - Clinical research coordinator

Qualified/Principal Investigator

Inspection

the act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources related to a clinical trial.

Adverse drug reaction (before market approval)

unintended response related to any done -must have probable cause`

Adverse drug reaction (after market approval)

unintended response used at NORMAL dosage

FDA Inspection process

- Evaluate facility Reiew regulatory records Review study participant records, compare data submitted to the FDA with the actual source records Have discussions with key ancillary personnel (laboratory techs, pharmacists, coordinators, sub-investigators Evaluate investigational product accountability and control Conduct an exit interview with the investigator by reviewing Form FDA 483, Inspectional Observations, if applicable, and providing feedback about the inspection observations

Regulatory Inspection -conducted by -purpose -outcome

- FDA - Verify data, assure compliance with regulations, and assure protection of research subjects - May affect the agency's decision to accept data supporting a marketing application. May have implications for the investigator if misconduct (for example, fraud, falsification, or fabrication) is found.

Sponsor Responsibilities

- Implementing and maintaining a quality management system -Designating qualified medical personnel who will advise on study-related medical questions or problems -Selecting investigators qualified by training and experience to properly conduct the study -Ensuring research is sound -Prep of documents

Monitor -conducted by -purpose -outcome

- Sponsor - Critical ongoing component of conducting a clinical trial - Assess and assure compliance with the study protocol on an ongoing basis

Audit -conducted by -purpose -outcome

- Sponsor or CRO - Quality assurance measure to verify data integrity and clinical trial processes - May result in SOP changes and/or recommendations for the monitoring process.

Adverse Event

- any unfavourable/unintended change - no causal relationship needed - may occur during or after administration of the investigational product

3 results of FDA Inspection

-No Action Indicated - Voluntary Action Indicated - Official Action Indicated

Investigator must report all SAEs within _____ to sponsors -if life threatening:

24 hours -immediately

Monitoring Plan

A document that describes the strategy, methods, responsibilities, and requirements for monitoring the trial.

Investigational new drug

A new drug, antibiotic drug, or biological drug that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes

Investigational Product

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way DIFFERENT from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use

An "Audit" is defined by ICH E6 as: An institutional self-assessment reported to the sponsor. A systematic and independent examination of trial-related activities and documents. The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources related to a clinical trial. The act of overseeing the progress of a clinical trial.

A systematic and independent examination of trial-related activities and documents.

Audit

A systematic and independent examination of trial-related activities and documents.

Monitoring Report

A written report from the monitor or sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs.

In ICH E6, what is the difference between an adverse event (AE) and adverse drug reaction (ADR)? - There is no difference. - An adverse drug reaction is related to individual subjects in a study while an adverse event is related to groups of subjects in a study. - An adverse event is reported in a clinical trial and an adverse drug reaction is the term used in pre-clinical research. - An adverse drug reaction is a response to the investigational product and an adverse event may or may not be a response to the investigational product.

An adverse drug reaction is a response to the investigational product and an adverse event may or may not be a response to the investigational product.

Sponsor-investigator

An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject.

Which of the following is an important component of drug accountability? - Drug shipping and disposition records - Manufacturer's compounding procedures- - Patent expiration date - Environmental controls

Drug shipping and disposition records

Which of the following is part of a clinical site inspection? -Interview with research subjects -Interview with study staff -Interview with regulatory authorities -Interview with IRB/IEC/REB members

Interview with study Staff

According to ICH E6, who should explain the correct use of the investigational product(s) to each study subject and check, throughout the study, to see if each subject is following the instructions properly - Investigator or person designated by the investigator - Pharmacist - Only the qualified/principal investigator - Research review board

Investigator or person designated by the investigator

Who has the ultimate responsibility for the administration/dispensation of an investigational product at the clinical site - Qualified/Principal Investigator - Clinical research coordinator - Sponsor - Pharmacist

Qualified/Principal Investigator

A regulatory authority (for example, Health Canada or the FDA) sends a representative to evaluate a trial in order to assure protection of research subjects, verify data, and assure compliance with regulations. This is an example of: -Sponsor monitoring visit -Regulatory Inspection -Sponsor audit -IRB/IEC/REB review

Regulatory Inspection

Subject 311 has had elevated white blood cell (WBC) counts for the past two (2) study visits, with no clinical signs or symptoms. "Increased WBC count" is not listed in the Investigator's Brochure (IB) as an adverse event. The investigator should: - Immediately fax a handwritten serious adverse event report to the regulatory authority (for example, the FDA or Health Canada). - Repeat the laboratory tests until they return to normal before reporting. - Hospitalize subject for transfusion. - Report the elevated WBC to the sponsor as an unexpected adverse effect.

Report the elevated WBC to the sponsor as an unexpected adverse effect.

A monitor visits a site conducting a Phase III study for an investigational drug to treat depression. The monitor is surprised to see so many improperly completed case report forms (CRFs) by the study personnel. The monitor would likely take the following action: -Bring the matter to the regulatory authorities (for example, Health Canada and/or FDA). -Fire the non-compliant study personnel, replacing them with others who will follow the protocol. -Bring the matter to the IRB/IEC/REB. -Retrain, if necessary, the study coordinators on CRF filling procedures as outlined in the protocol.

Retrain, if necessary, the study coordinators on CRF filling procedures as outlined in the protocol.

When evaluating the causality of an adverse event, which of the following should be a consideration - The timing of the event in relation to administration of the investigational product - Whether or not the adverse event qualifies as a serious adverse event - The method used to randomize subjects - The number of planned interventions in the protocol

The timing of the event in relation to administration of the investigational product

A study subject reports that he has been having headaches for years but they seem to have become more frequent since starting the study. The investigator believes this is not related to the study medication. How would a clinical research coordinator document this event? - This event would be an adverse event because the complaint is more frequent headaches since starting the study. - This event would be a serious adverse event because the subject is taking part in a research study. - This event does not require documentation because it is part of the study subject's medical history. - This event would not be considered an adverse event, but it would be noted in the subject's medical history form.

This event would be an adverse event because the complaint is more frequent headaches since starting the study.

A study subject breaks his leg in a skating accident. Is this incident a Serious Adverse Event (SAE)? - No - it is not even an Adverse Event (AE). - Yes - if the subject stayed in hospital overnight or had serious complications. - No - it was not related to participation in the study. - Yes - only if the subject withdrew from the study.

Yes - if the subject stayed in hospital overnight or had serious complications. ANY medical occurrence at ANY dose resulting in HOSPITALIZATION

Unexpected Adverse Event

adverse reaction, the nature or severity of which is not consistent with the applicable product information

Sponsor

individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial

Serious Adverse Event

reaction that results in: -death -life threatening -requires additional hospitalization -disability -birth defect

sponsor duty for SAEs

report to SUSARs