CCRP

Parallel study design

Used to compare a new treatment against a control group

Example of Quality Assurance

Auditing

Who is responsible for submitting reports for medical device adverse events and product problems to the FDA?

manufacturers, device facilities and importers

Document that summarizes the known information about the investigational product

IB

If the IRB agrees with the NSR status, what are the next steps?

Sponsor sends IRB approval, device description, rationale for NSR, and protocol to the FDA

If sponsor determines the study is NSR, what are the next steps?

Sponsor submits device description and rationale for NSR status and protocol to investigator > investigator submits materials to IRB

The primary goal of the IRB is

to protect the right and safety of human subjects

Crossover study design

two or more treatments are given sequentially to the same subject

Emergency Use (expanded access)

* Life threatening condition *No alternative and no time to get FDA approval *must be reported to sponsor *must be reported to IRB within 5 days of use

Example of Justice

Appropriate selection of panelist

What type of medical devices require PreMarket Approval Application (PMA)

Class III

Responsibility for the investigational product ultimately lies with who?

Investigator

An NDA is submitted after what?

Phase III

Who submits form 1572 to the FDA

sponsor

Sponsor must submit IND Safety Reports with in _____ days after knowing of an event meeting reporting criteria

15 calendar

Contents of IB (5)

- drug formulation and substance -pharmacological and toxicological effects -pharmokinetics and biological disposition -safety and effectiveness in humans -possible risks and side effects

Examples of Special Controls for Class II Medical Devices

- labeling requirements -post market surveillance -mandatory performance standards

Phase II Drug Studies

- multicenter -small # of subjects, combined population -obtain short term safety data

Labeling Requirements

-Name and place of manufacturer -Quantity of contents -Caution Statement -All relevant hazards, warnings, known adverse event reactions -

If FDA requests additional information, sponsor must submit that information within _____ days after receiving the request

15 calendar days

3 main parts to belmont report

1. Boundaries with practice v research 2. Ethical principles with benefince, justice, respect 3. applicaitons

4 things needed from the investigator prior to the start of the clinical trial

1. FDA Form 1572 2. CV 3. Financial Disclosure Form 4. Protocol

UADE in medical device trial

10 working days for both sponsor and investigator

3 primary responsibilities of an investigator

1. Oversees the conduct of the clinical trial 2. Protects the rights, safety, and welfare of subjects 3. Control the use of investigational product

4 components needed for consent using short form

1. short form consent document 2. oral presentation of ic 3. an irb approved written summary 4. witness

Sponsor must report the results of an unaticipated device AE to investigators and IRB's within _______ working days of learning about the AE

10

When should investigator report SAE's for a medical device trial

10 working days

How long must the investigator retain the IRB correspondence, research records and signed consent documents for?

3 years after completion

Time requires for IRB record retention

3 years after study completion

How long does pre-clinical research usually take

3-6 yrs

How long does the FDA have to review the IND application

30 days

Minimum of IRB members needed

5

IDE Reporting - Withdrawl of IRB or FDA approval happens within how many working days?

5 working days

IDE Reporting - Must report the current list of investigators how often?

6 months

Sponsor must notify the FDA within _______ days after sponsor is notified of unexpected fatal or life threatening adverse events.

7 calendar days

Sponsor

An entity that initiates a clinical investigation

An IND is submitted after what?

Basic Research, Pre-Clinical Discovery

Two common tools for reducing bias

Blinding and Randomization

What is a process that is used to identify root causes of issues or problems and actions to resolve them?

CAPA

FDA Form 1571

Cover page of an Investigational New Drug application (IND) *must be filed by the sponsor

510k Clearance Submission or PMN (premarket notification)

Device manufacturer must notify FDA 90 days prior to marketing a device

Significant Risk Device Study

Device that presents a potential for serious risk to the health, safety, or welfare of a subject.

Essential documents (know definition)

Documents that permit evaluation of the conduct of a trial and the quality of data produced

When must the investigator update the IRB about the progress of a trial?

During the study and at study termination

How long must the investigator provide financial disclosure reports to the sponsor for?

During the trial and one year after completion

If the research involves no more than minimal risk or there were just minor changes in previously approved research ( 1 year or less) what kind of IRB review can happen?

Expedited Review

In an SR study, who must approve the IDE application prior to the study start?

FDA

Certification that no financial interest exists

FDA Form 3454

Disclosure of financial interestes

FDA From 3455

Regulatory Class 3

Highest Risk, pre market approval usually required, and clinical trials required

What 2 things are required before a device study can begin?

IDE and IRB approval

Who provides ongoing approval for continuation of the study continuation at the site

IRB

When should investigator report SAE's for a drug trial

Immediate to sponsor Promptly to IRB (no specific time)

Drug study - When does the investigator need to report any serious adverse events to the sponsor? Device studies -

Immediately to sponsor 10 working days

Example of respect for persons

Informed Consent

What allows a medical device that has not received marketing clearance or approval to be shipped for use in a clinical study without complying with other regulations

Investigational Device Exemption

In medical device studies, what is used by investigators instead of 1572?

Investigator Agreement

Predicate Device

Legally marketed device to which equivalence is drawn

Regulatory Class 1

Lowest Risk, clinical trials not usually required ex. bandaid

Sponsor requirements in NSR Study:

Maintain records Ensure investigator maintains records Obtain IRB approval Consent Reports

Regulatory Class 2

Moderate Risk, usually requires 510k Might require pre market approval

Example of Quality Control

Monitoring

What is filed when the sponsor considers that there is sufficient information to meet the regulatory requirements for approval

NDA

In an NSR study, do sponsors and IRB's have to report to FDA prior to the study starting?

No

Timeline of 3 historical events

Nuremberg trials > Declaration of Helinski > Belmont Report

What phase determines the drugs pharmokinetics and pharmodynamic profiles?

Phase 1

What phase of a drug study is the INITIAL DEMONSTRATION of efficacy in subjects with the condition under investigation?

Phase 2

What phase of a drug study is CONFIRMATION of short term efficacy and safety?

Phase 3

What phase of a drug study continues to assess overall value and surveillence for less common AE's?

Phase 4

QA

Planned and systemic actions that are established to ensure the trial is performed Focuses on prevention

Medical device reporting

Post market surveillance used by the FDA to monitor device related safety issues

Long-term toxicology of an experimental drug in animals most likely refers to which part of drug development?

Pre-clinical

Non-Clinical Research

Pre-clinical development/stage of research before testing in humans (included animal and in-vitro testing)

Example of beneficence

Risk/Benefit Analysis

All medical devices will fall under what 3 categories?

SR NSR IDE Exempt

Studies that involve an implant are significant risk or non-significant risk?

Significant Risk

What are the only type of devices that require an ide application to the fda?

Significant Risk Devices

Who files the IND Application?

Sponsor

Who is required to provide written IND safety reports to all investigators and the FDA?

Sponsor

Who is the responsible party for the clinical trial conducted under its initiation and oversight?

Sponsor

Who makes the initial determination whether it is a SR or NSR study?

Sponsor

Who's main responsibility is to ensure overall clinical trial conduct is in compliance with it's regulations

Sponsor

Who does the investigator report adverse events to?

Sponsor (not the FDA)

FDA Form 1572

Statement of Investigator Form - Signed Declaration from investigator that he/she will comply with FDA regulations

Randomization

Subjects are randomly assigned into different treatment arms

Indications for Use

The disease or condition that the device will diagnose or treat

Intended Use (Medical Device Study)

The general purpose of the device or its function

IDE (Investigational Device Exemption)

The mechanism the sponsor uses to submit documents to the FDA

True or False - Progress reports have to be submitted to the FDA yearly for a SR study

True

True or False The investigator must submit a new Form FDA 1572 to the sponsor when an investigator is participating in a new protocol that has been added to the IND or when a new investigator is added to the study.

True

True or False: IRB can waive informed consent in an NSR study if the risk is minimal

True

True or False: IRB approval of the short form consent document and written summary is needed prior to usage

True

True or False: IRB must review greater than minimal risk at least annually

True

for FDA 510k clearance submission, __________ must notify FDA at least _______ days prior to marketing a device?

a. device manufactureer b. 90 days

Order of new drug development

basic research > drug discovery > pre-clinical > IND > phase i,ii,iii > NDA > fda review and approval > phase 4

QC

ensures quality in the end result Focuses on identification and correction

SAE Reporting in Drug Trial (investigators and sponsor)

investigator - immediately reports to sponsor sponsor - 15 calendar days after learning of risk

Blinding

method where personnel involved in the trial are intentionally blinded from knowing the treatment assignment of each subject

Approved IDE

permits a device to be shipped lawfully for the purpose of conducting investigations of the device

Belmont Report

principle of justice requires equality in research conduct (burdens and benefits are shared fairly)