Coordinator Responsibilities Renee LeBlanc, RN CTSO Manager ITHS - - PDF document

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Coordinator Responsibilities

Renee LeBlanc, RN CTSO Manager ITHS Education Series

Friday Night

Get to go to Dinner  Cohort log tells you if an assignment is available for subject 4  AE logs current for subjects 1- 3  Enrollment log confirms no DLTs for subjects 1-3  Study calendar confirms subjects have passed

• bservation period

 Preprinted orders are ready to be signed, kits prepared Get to Stay Late  Must read protocol to determine cohort plan; discover inconsistencies  Must review source and extract AEs for subjects 2 and 3 to determine if there have been DLTs  Must determine start dates and calculate day on study to see if

• bservation period is complete

 Must hand write orders  Search through supplies to make kit—out of supplies  Computer crashes, shuttle delayed

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Objectives

Improve your Understanding of the Study Coordinator Role and Responsibility for Promoting patient safety Supporting protocol compliance Producing quality data

Purpose of Attending

A strong foundation of understanding the application of the principles of GCP is assurance of subject protection Act purposefully with sound judgment Respond to challenging situations with best options Confidence defending your actions to monitors and auditors

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Subject Safety

Focus on Priorities

To minimize risk Consent Eligibility Safety labs AE CRFs Protocol adherence unless to avoid immediate harm Quality data

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What if?

 Adult subject determined eligible for study while under conscious sedation. Mother thinks it’s a great study and signs the consent. Autonomy?  New risk language is known to the PI but IRB will not review prior to subject appointment  Subject needs blood draw for eligibility; PI wants standard care labs resulted before clinic visit to determine if pt can start chemo on or off protocol.

The Regulations

 45 CFR 46 (aka “The Common Rule”) gives requirements for consenting and documentation of consenting for research  21 CFR 50 Protection of Human Subjects 50.24 lists the basic elements of informed consent. 50.20 General Requirements of Informed Consent  21 CFR 312.60 General Responsibilities of Investigators, “An investigator shall,…, obtain informed consent…”  ICH GCP Guidelines 4.8 Informed Consent of Trial Subjects

 4.8.7 …provide the subject with ample time…

 Institution policy and procedure

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How Coordinators Support Subject Safety

 Participate in the informed consent process; ensure adequate time and access to personnel qualified to answer questions in order that the subject can make an informed decision.  Schedule follow up appointments if necessary  Ensure subject’s questions are answered  Ensure documentation of the process  Reconsent if new information or procedures  May need pre-research lab consent to determine eligibility and stay in compliance (HAMA)

Informed Consent

Know the Dos  Sign the most current version  Process conducted by licensed personnel  Document process  Consent prior to study procedures  Re-consent when new risk and procedures What went Wrong  (Paper) consent in drawer expired  Physician not available to sign consent document  Process started by left off with indecision; dates don’t match  Blood draw before clinic appointment  Subject has left system

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Coordinator Responsibilities

What went wrong  (Paper) consent in drawer expired  Physician not available to sign consent document  Progress notes indicate subject undecided  Signature dates don’t match  Blood draw before clinic appointment  Subject has left system Corrective Action  Team utilizes central file with current documents  Develop a process to include PI in follow up consent  Document subject gave informed consent  Note file explaining date discrepancies  Research lab blood draw consent  Letter to subjects

Read what you sign

 “I have reviewed the risks, benefits and alternatives of the study with the subject and answered all their questions satisfactorily.”  This is a statement for a licensed personnel to sign such as a physician, physician’s assistant

• r advanced practice nurse—with study specific

training documents on file

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What if?

Subject’s neutrophil count lower than protocol requirements for treatment. Treat and support with GCSF? Subsequent infection Renal function above parameters, hydrate and give Cyclosporine. Renal failure Under additional scrutiny when participating in research

How Coordinators Support Subject Safety

Confirm eligibility criteria are met prior to enrollment —document review and sign off by PI. Ensure any deviations from the eligibility are approved by the PI/sponsor and

• documented. Noncompliance may need

to be reported; depending on institution. Ensure protocol evaluations are done; visit checklists, review labs.

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Regulations

 Determination of risk and benefit is ongoing  CFR 45 Part 46

IRB approval of research section 46.111 Risks to subjects are minimized…the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects…

 GCP 2.2

A trial should only be initiated and continued if the anticipated benefits justify the risks

How Do We Know if the Risk Benefit Ratio has changed?

By review of AE trends: change in the frequency or severity of the expected AE Outcome data. Study showed no difference between groups and hypothesis was a 20% difference in the new treatment Poor enrollment: is the study question going to be answered

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Adverse Event Tracking

Get a good baseline AEs can be Expected or Unexpected

Review expected AEs to determine if trends indicate a change in the initial risk benefit ration DLTs will result in changes to the subject’s treatment plan and contribute to study stopping rules therefore real time AE collection is necessary

PI review and sign off documented

What is the protocol DSMP?

Examples:  Adverse experiences will be graded and recorded throughout the study according to NCI CTCAE, version 4.0.  Toxicities will be characterized in terms including duration, intensity, and time to onset.  Only grade 2 and higher adverse events or adverse events will be recorded.  AEs will be collected until…

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CTC V3 Grade 3 Neutropenia

CRFs/Data Collection Priorities

 Baseline  Eligibility checklist  Adverse Events  Log tracking stopping rules  Study Drug/Intervention  Response  End of Study: is the subject evaluable Note: Not on the list: CRFs for labs, con meds. PI initiated studies: consider printing from ORCA and filing in research chart vs. transferring data to CRF

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Reminder for studies with DSMB

Coordinator Responsible for:  Scheduling per protocol: failure to conduct DSMB meetings = noncompliance  Maintain a log with meeting dates  File minutes and submit to IRB/FDA  Response and follow up

Modification/Unanticipated event

 DSMB charter defines quorum, includes contact information and purpose of meeting

Real Life: Don’t Try This at “Home”

 PI signs off on eligibility after the subject has been on study for a month  Subject comes in for a study blood draw, PI not around to sign consent…coordinator signs for investigator  Baseline liver function labs surprisingly show subject not eligible, unfortunately labs not verified prior to start of study procedures  Glucose level is close enough to the protocol cut

• ff of go ahead and treat

 Sterility test results are not available and the study drug is about to expire-proceed

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Quiz

A subject presents at the clinic who does not meet the protocol eligibility criteria. The coordinator A) Informs the PI, “(but) the protocol says…we will need to inform the IRB” B) When asked by the PI if the protocol will exclude the subject says, “I don’t know.” C) Says, “Whatever you think is best.”

Compliance

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Protocol Development

 Read the protocol for consistency between sections  Identify operational issues –prepare lab requisitions  Compare protocol, consent and contract to ensure consistency—important for billing too  Meet with the PI to determine what procedures are standard of care and which are research  Confirm eligibility criteria, stopping rules and cohort assignment plan with PI

If you don’t

Confusion about which instructions to follow: fuel for debate with monitors Noncompliance/Protocol Deviations to report Protocol Modifications to correct discrepancies and inconsistencies Compromise study data for missed labs Research billing errors

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45 CRF 46

IRB is required to have written procedures that require the prompt reporting to the IRB of proposed changes in approved research activity, and for ensuring that such changes…may not be initiated without IRB review and approval EXCEPT to eliminate apparent immediate hazards to the subject

OHRP

 Continuing noncompliance is reportable to

• utside government agencies

Institutional lawyers care if you don’t follow the protocol

 45 CRF 46: IRBs are required to have written procedures to ensure prompt reporting to the IRB, to the department or agency head of any unanticipated event that involves risk to subjects

• r others or any serious or continuing

noncompliance with this policy or the requirements or determinations of the IRB

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How Coordinators Support Compliance

 Help write a protocol that can be implemented, consistent and clear  Communicate with clinic staff: develop tools that help them comply  Checklists: make sure they match the protocol  Track events--renewals  Pre-printed study specific orders  Manual of operation

Labs and multicenter trials

Version Control

 Central files utilized for current documents  Electronic files labeled: Current Documents  Documents with dates: version # or date of approval  Document management: what updated, when, why, how manage previous versions-replace vs. going forward  Archive previous versions  PI approval of new documents  Use of expired documents = Noncompliance, inconsistent data

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Examples

PI cuts and pastes from a borrowed protocol for an oral version of the drug. Protocol requires daily IV hydration; not applicable to oral drug. Stopping rules for all grade 2 AEs related to study drug– study stopping rules met for

• hyponatremia. Clarify clinically significant

Protocol Deviations

Avoid  Protocol specific

• rders were in place

 Labs missed but coordinator noticed and added to next draw  Visit checklist Inevitable  Long list of labs, not

• n standard panel

 Unaware that labs were missed  No checklists  Note: Labs missed on several visits = continuing noncompliance

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Clinical vs. Research

 Individual patient needs may conflict with the protocol  Clinician and Researcher conflicts of interest  http://www.nytimes.com/2010/09/19/health/resea rch/19trial.html?_r=1&scp=1&sq=clinical%20trial &st=cse  Research is to obtain generalizable knowledge  Flexibility in the protocol helps

Quality Data

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GCP

2.10 All clinical trial information should be recorded, handled and stored in a way that allows its

• 1. accurate reporting,
• 2. interpretation and
• 3. verification

How Coordinators Support Quality Data

 Source meets ALCOA criteria  Source data is Verifiable  Errors are corrected  Organized Files  Inconsistencies and unusual events are clarified in notes to file  Data collection plan; consistency Did you know-Poor data is a risk to subject?

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ALCOA Test

Attributable Legible Contemporaneous Original Accurate

ATTRIBUTABLE

• Means belonging to. The data should be

attributable in regards to both the identity of the individual responsible for making and recording the observations as well as identify the source of the observation. (this implies signing data entries) LEGIBLE

• The data should be readable in every sense. This

includes recording it indelibly on durable media. This applies to electronic records as well. CONTEMPORANEOUS

• The data should be recorded as close in time as

possible to the time the actual event being recorded occurred. (This implies a need to date entries)

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ORIGINAL

• First recordings are always the highest quality. The

more times data is copied the lower quality it becomes and the greater the chance for transcription and copying errors, thus affecting the last element of quality—accuracy. ACCURATE*

• Correct and true.

*Why we obtain lab certifications. Why some data needs to come from staff with specialized training.

AE collection

What grade for how long? What are expected events? Review labs, progress notes Document PI determination of relationship and expectedness

Expedited or annual

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AE reporting

Required to report trends that indicate new risk to subjects or change in the risk benefit ratio

Prioritize AE reporting PI review and sign off Plan for CRR review, DSMB, IND annual reports

New Monitor Arrives for Site Visit

Who created this data? When were the vitals signs taken? What was the IRB response to the noncompliance report you submitted last month? When did you make CRF changes? Was the PI aware/approve the CRFs? Notice different questionnaire for subject 1

• vs. 5.

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See Samples of Quality Data and Non-Attributable Data

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Best Practice

Inherited a Study under an IND

When is the annual report due? Was the last SAE submitted to the IND? Was the last protocol amendment submitted to the IND? Did the FDA receive the CV for the new investigator? What was the last serial number? Was the FDA informed of the deviation?

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Best Practice… ……Lawyers Nightmare

 Log lists all submissions to FDA with 1571; initial submission

Coordinated submissions to avoid error in numbering

 Fed Ex Receipts on file  Annual reports completed on time  Drawer full of unlabeled files out of chronological order  Missing files  Duplicates  No Fed Ex Receipts  1571 forms are missing, inconsistent  Annual reports are late

Develop study logs

 Regulatory file logs; what was submitted, approved  Delegation log (start and end dates/PI initials)  Enrollment log: AEs that contribute to stopping rules, who received drug, screen failures

IRB/FDA/Sponsor all have same enrollment number

 Consent log: versions that require reconsenting, multiple logs for study, pediatric subjects- reconsent adults  Death, withdraw logs  Deviation log

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Develop checklists

Visit checklist to ensure protocol required labs and assessments are done

Investigator initiated studies may not need a CRF to capture vitals, conmed or labs

Enrollment checklist: Completed and signed off PRIOR to initiation of study procedures Procedure checklist

Scope of Practice

Work within your scope of practice UW Credentialing—update if taking on new tasks Document delegation of tasks

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Letter from the UW Credentialing Office will state:

 “Privileges apply only to your current position and role description as outlined in your application. Revocation of your privileges can result from a change in your position

• r role without informing us and/or expiration of licensure

required for your position or role. Confirmation of a renewed license must be submitted to the credentialing

• coordinator. Additionally, proof of current TB status must

be submitted to the credentialing coordinator annually. You must contact the credentialing coordinator 1 month prior to expiration to obtain renewal materials.”

Managing the Study Team

Protocol eligibility: Karnofsky missing; follow up with the clinic team Knowledgeable about standard of care; anticipate problems. Information sheets Knowledgeable about disease; expected AEs Participate in Protocol Implementation; nurse education

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Don’t Forget to Document Training

Document training: GCP, Human Subjects Instructed in the conduct of protocol Instructed in consenting subjects Study specific: specimen processing See Resource Slides for Training Opportunities

Questions? Discussion?

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Resources for Coordinator Tools

 Institute for Translational Health Sciences http://www.iths.org/  FHCRC Web Research Process and Resource Guide http://www.cancerconsortium.org/rto/training/res

• urce_guide/index.html

 UW Clinical Trials Handbook

https://www.washington.edu/research/clinical-research- handbook// Need UW Net ID

Resources to Learn about Diseases

National Cancer Institute

http://www.cancer.gov/

American Cancer Society

http://www.cancer.org/

National Institutes of Health

http://www.nih.gov/

Center for Disease Control & Prevention

http://www.cdc.gov/

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Resources for Adverse Event Coding

NCI/NIH Common Terminology Criteria for Adverse Events (CTCAE)

http://ctep.cancer.gov/protocolDevelopment/ele ctronic_applications/ctc.htm

Resources

ACRP http://www.acrpnet.org/ Resource Library—need membership password Site Manager’s Forum: SOP template