“So You Think You Know GCP …” Session S794 Jill Matzat, RN, BSN, CCRA, CCRT President, Medical Research Management & CRA Solutions, Inc. Paul Below, CCRA,

““So You Think You So You Think You Know GCP …”Know GCP …”

Session S794

Jill Matzat, RN, BSN, CCRA, CCRTPresident, Medical Research Management

& CRA Solutions, Inc.

Paul Below, CCRA, CCRTClinical Research Consultant, P. Below Consulting, Inc.

DisclosureDisclosure• Jill Matzat and Paul Below

have no relevant financial relationships in relation to this educational activity

BackgroundBackground• This presentation was developed to counter

numerous misconceptions and myths about Good Clinical Practice overheard by the presenters during their careers

• This presentation is intended to teach GCP concepts using a quiz format (audience polling is available via text message voting)

Learning ObjectivesLearning Objectives• Define Good Clinical Practice (GCP)

• Differentiate between FDA requirements (stated in regulation) and FDA recommendations (stated in guidance documents) in several key areas

• Identify several circumstances where “industry best standard” practices exist that go above and beyond what the FDA requires and even recommends

What is Good Clinical Practice?What is Good Clinical Practice?• Good Clinical Practice (GCP) is a unified

standard for designing, conducting, recording, and reporting trials that involve human subjects

• GCP is composed of many parts that cannot be foundin any one book or place

GCP

Other Federal Regulations

FDA Regulations(21 CFR)

State Law

Local Law (Institutional

and IRB Policies)

FDA GuidanceDocuments

ICH Guidelines for GCP

Sponsor SOPs

IndustryBest Practices

So You Think Know GCP …So You Think Know GCP …• The following slides are a series of questions to

test your knowledge of GCP

• You will be able to submit your answers via text messaging

• All answers areanonymous (no oneis identified by name or phone number)

How To Vote via TextingHow To Vote via TextingExample Question: What is your favorite color?

• Blue (72612)

• Red (72613)

• Green (72614)

• Yellow (72615)

To vote, text the corresponding keyword to 22333

NOTE: Standard text messaging rates apply.

Some Notes on TerminologySome Notes on Terminology• “The FDA requires” = it is specified in regulation

• “The FDA recommends” = it is specified in an FDA guidance document

Informed Consent QuestionInformed Consent Question

FDA regulations require the following:

Answer Keyword

The ICF must be signed by the subject 239432

The ICF must be signed by the person obtaining consent

239433

The ICF must be signed by the investigator 239434

Every page of the ICF must be initialed by the subject

239435

All of the above 239436

Text your answer (keyword) to 22333


Answer Keyword

The ICF must be signed by the subject 239432

The ICF must be signed by the person obtaining consent

239433

The ICF must be signed by the investigator 239434

Every page of the ICF must be initialed by the subject

239435


Per 21 CFR 50.27, the informed consent form should be “signed and dated by the subject or the subject's legally authorized representative at the time of consent”

However, FDA guidance (ICH GCP) also recommends that the form be signed by the person obtaining the consent

Other ICF MisconceptionsOther ICF Misconceptions• It is acceptable for the study staff to date the

consent for the subject if they forgot to do so

• A spouse can always function as a “legally authorized representative”

• Consent forms must be written at a 6th grade reading level

Form FDA 1572 QuestionForm FDA 1572 Question

FDA guidance recommends the following:Answer Keyword

The signed 1572 must be submitted to the FDA prior to the Investigator’s participation in the trial

236113

The 1572 must be updated when new sub-investigators are added to Box #6

236114

The Principal Investigator must be a physician 236115

Only one Principal Investigator should be listed in Box #1

236116




The signed 1572 must be submitted to the FDA prior to the Investigator’s participation in the trial

236113

The 1572 must be updated when new sub-investigators are added to Box #6

236114

The Principal Investigator must be a physician 236115

Only one Principal Investigator should be listed in Box #1

236116


A recent FDA Guidance Document was issued in May 2010 to clarify the agency’s expectations regarding completion the form.

Other 1572 MisconceptionsOther 1572 Misconceptions• Must be completed on a double-sided form

• Must be typed

• Study Coordinators should not be listed as Sub-Investigators in Box #6

• All rotating study staff (e.g., residents, fellows) must be listed as Sub-Investigators in Box #6

Curriculum Vitae (CV) QuestionCurriculum Vitae (CV) Question


Answer Keyword

CVs must be collected for all investigators (PI and all Sub-investigators)

239968

CVs must be collected at the beginning of the study

239969

CVs must be “up-to-date” 239970

CVs must be signed and dated by the completer

239971




Answer Keyword


239968


239969



239971


Per 21 CFR 312.23 (a)(6)(iii)(a), Sponsors need to include in their initial IND submission a statement of the qualifications (curriculum vitae or other statement of qualifications) of each Principal Investigator and only the names of each Sub-Investigator


Answer Keyword


239968


239969



239971


However, FDA guidance (ICH GCP) recommends that the Investigator CV be “up-to-date” (4.1.1) and be collected for all PIs and Sub-Investigators (8.2.10)

Case Report Form QuestionCase Report Form Question


CRF corrections should be dated and initialed and should not obscure the original entry

241939

When CRFs are used as source documents, they should be specified in the protocol

241940

Sponsors may make changes to the CRF data with the authorization of the investigator

241941


None of the above 241943




241939


241940


241941


None of the above 241943All of the above are specified in ICH GCP



241939


241940


241941



There is nothing in FDA regulation or guidance that specifies that CRF corrections must be made with a single line through the original entry

Investigational Product Investigational Product QuestionQuestion


Answer Keyword

Investigational product (IP) must be stored in a secure location with limited access

239961

IP must be environmentally monitored and controlled

239962

IP must be labeled with “Caution: New Drug (or Device) -- Limited by Federal (or United States) law to investigational use.”

239963

All unused IP must be returned to the sponsor at the end of the trial

239964



Answer Keyword


239961


239962


239963


239964

Labeling requirements are specified for drugs in 21 CFR 312.6 and for devices in 21 CFR 812.5


Answer Keyword


239961


239962


239963


239964

The only language in the device or drug regulations related to IP storage concerns investigational drugs that are controlled substances (21 CFR 312.69, “storage of the investigational drug in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited …”)


Answer Keyword


239961


239962


239963


239964

21 CFR 312.59 indicates sponsors “may authorize alternative disposition” for unused investigational drugs

21 CFR 812.110 indicates that investigators can “otherwise dispose of the device as the sponsor directs”

Emergency Use of IP Emergency Use of IP QuestionQuestion

If IP is used in a life-threatening situation prior to obtaining informed consent, what is the required time frame to report this to the IRB?

Answer Keyword

Promptly 241377

Within 24 hours 241378

Within 3 calendar days 241379

Within 3 working days 241380



If IP is used in a life-threatening situation prior to obtaining informed consent, what is the required time frame to report this to the IRB?

Answer Keyword

Promptly 241377

Within 24 hours 241378

Within 3 calendar days 241379



Reporting requirements for all products are specified in 21 CFR 50.23: “shall be submitted to the IRB within 5 working days after the use of the test article”

Regulatory Document Regulatory Document QuestionQuestion

FDA regulations require that the following documents be signed by the investigator:

Answer Keyword

Trial Delegation Log 241496

Completed and final case report forms 241497

Financial disclosure forms 241498

Protocol signature pages 241499




FDA regulations require that the following documents be signed by the investigator:

Answer Keyword

Trial Delegation Log 241496

Completed and final case report forms 241497

Financial disclosure forms 241498

Protocol signature pages 241499



The only document specified by FDA regulation that must be signed by the investigator is the Form FDA 1572 (for drugs) or the Investigator Agreement (for devices)

Closing ThoughtsClosing Thoughts• Most FDA requirements are vague and open to

some interpretation

• Most of what we do in clinical research is driven by our own industry best practices and not FDA requirements or even recommendations

• Be careful when telling an investigator site, “You have to do this because the FDA requires it” unless you are certain that it is specified by regulation

Poll ResultsPoll Results• Complete poll results are available at:

www.pbelow-consulting.com/ACRP2011.html

Your Chance to Ask Us QuestionsYour Chance to Ask Us Questions

Contact InformationContact Information• Jill Matzat

[email protected] visit Jill at the Medical Research Management booth in the exhibit hall

• Paul [email protected]

Paul presents again on Monday at 4:15 pm (S831 - You've Discovered Fraud - Now What Do You Do?)

Poll results available at www.pbelow-consutling.com/ACRP2011.html