how to set up a clinical network group

8/14/2019 How to Set Up a Clinical Network Group

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How do you establish a sickle cell

disease network?

Michael R. DeBaun MD, MPH


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Outline

Silent Cerebral Infarct Trial as an example

Code of Federal Regulations (ICH)

Local Regulations Responsibilities of the Investigator

Serious Adverse Events Notebook setup/Manual of operations

Data quality assurance Chart preparation

Audit preparation


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Teachers Questions

Fall 1991

What is wrong with this child?

Can you tell me if this is going to happenagain?

What can you do to treat this child?

What can I do to help this child learn?


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Patient Case

Fall 1991ID: 8 y/o BF with SCA

Chief complaint: Forgetting

Informant: 3rd grade teacher

HPI: Pts teacher reports that patient is unable

to remember skills that were mastered three

months ago

Exam: Normal


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SLCH Sickle Cell Disease Stroke Team

1991- 2008

Neurologists: Tracy Glauser, Michael Noetzel

Psychologists: Susan Craft, Jeff Schatz and

Desiree White

Radiologist: Marilyn Siegel Neuroradiologist: Robert McKinstry

Hematologist: Allison King


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SLCH Stroke Group

Silent strokes are not detectable by neurologists

J Child Neurol 1995;10:88-92

Location and size of strokes and silent strokes

influences the magnitude of cognitive deficits

J Child Neuropsychol 1999; 5(2):92-103 J Child Neurol 2002;17:891-895

Working memory deficits are associated with silent

strokes

J Clin Exper Neuropsychol 2000; 22(2):257-264

Reversible posterior leukoencephalopathy is distinct

entity in SCD and is not necessarily a cerebral infarct

Blood 2002;101(2):415-419


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Evidence to Support the

Significance of Silent Strokes

Prevalent ~20% of students

Gradient in global IQ

Associated with poor school performance

Progressive neurological complications


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Funded 2003, N INDS


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Silent Cerebral Infarct Transfusion Trial:

Multi-Center Clinical Trial

Primary Hypothesis:

Prophylactic blood transfusion therapy inchildren with silent cerebral infarcts willresult in at least 86% reduction in the

proportion of patients with clinically evidentstrokes, new or progressive silent cerebralinfarcts


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SIT Trial Participating Sites

(n=25)

Clinical Sites

Imaging & Reading

Biorepository


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Perspective of the Study From of

View of the Student and Parents Two MRIs of the brain to detect silent stroke and

progression

Pediatric neurology evaluation-annually

Three cognitive tests performed over three yearsallowing augmentation of IEP

In the transfusion arm monthly blood transfusion for three years

In the observation arm visit to hematology clinic every three months for three

years


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Mar

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Jun-05

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0

50

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150

200

PatientsRand

omized

Number of Patients Randomized in SIT TrialProjected and Actual

Projected

Actual

Current: 138

5/20/08

Goal: 204


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Code of Federal Regulations ICH

guidelines

http://www.fda.gov/cder/guidance/iche3.pdf

International Conference on Harmonisation International ethical and scientific quality

standards for trials that involve the participation of

human subjects

Federal and institutional requirements

Sponsor requirements
http://www.fda.gov/cder/guidance/iche3.pdfhttp://www.fda.gov/cder/guidance/iche3.pdf


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Local Regulations

HRPO website:

https://hrpo.wustl.edu

Screening Log

To help establish potential in screening for

eligible participants

Required by HRPO annually
https://hrpo.wustl.edu/https://hrpo.wustl.edu/


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Example of Federal vs Local

Regulations Local audit requirement

Source documents (paper copy) of all standard

care blood work should be attached to CaseReport form

No Federal requirement


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Responsibilities of the

Investigator Obtain Informed consent

Conduct Study

Manual of Operations Obtain and maintain appropriate training

Hire and supervise qualified staff

Report adverse events/Serious Adverse events

Maintain fiscal responsibility


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Additional responsibilities

Ensure all study staff have completed CITI

training (HRPO website)

Also training with respect to the protocolinvestigational procedures or products.

Delegate duties to qualified staff

Support the safety monitoring process


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Ethics protocol

Arbitrary how detailed you want it to be.

Should give overview of your study


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Manual of Operations

Very detailed protocol outlining each study

procedure


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Example of Ethics vs. MOP protocol details

HRPO protocol states: Weight will be measured at baseline visit

Manual of Operations states:

Follow the steps below to measure the childs weight: The child will be barefoot or wearing thin socks

and will wear light clothing, ideally a tee-shirt andshorts.

Zero the scale

The child will stand in the middle of the platformduring the measurements.

Weight the child and record the value on the datacollection form.


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Serious Adverse Events

www.hhs.gov/ohrp/policy/AdvEvntGuid.htm

Federal regulations refer to unanticipated

problems involving risks to participants orothers (45 CFR 46.103(b)(5)).
http://www.hhs.gov/ohrp/policy/AdvEvntGuid.htmhttp://www.hhs.gov/ohrp/policy/AdvEvntGuid.htm


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Getting Started

Manual of Operations

IRB protocol

Study forms/Data coordinating center


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Definition of a Serious Adverse

eventUnanticipated problems involving risks to

participants are defined as untoward

events that are serious, unexpected, andreasonably related to the research.


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Serious

An event is defined as being serious if the eventadversely alters the relationship between risks and

benefits and includes events that either result in orrequire intervention to prevent:

Inpatient hospitalization or prolongation of hospitalization

Life-threatening reactions

Result in persistent or significant disability/incapacity orpermanent harm or disability (either physical or psychological)

Jeopardize the subject

Congenital anomaly/birth defect in the offspring of researchparticipant

Breach of confidentiality that may have a negative consequence

Death


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Unexpected

An event is defined as being unexpected if

the event exceeds the nature, severity, or

frequency described in the protocol or theInvestigators Brochure


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Reasonably Related An event is defined as reasonably related to

the research if it is more likely to be caused

by the research procedures than not.


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Serious adverse events-Time line

Death

*Immediately

Changes to the protocol made without HRPO approval to eliminate

apparent immediate hazards to a participant*Within five (5)calendar days

Life-threatening

*Within seven (7) calendar days

Occurring in a study with an investigational device

*Within ten (10) working days

All other events

*Within fifteen (15) calendar days


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Informed consent

Assure HRPO stamp on every consent

Future sample use

Pregnancy box

Time of consent

Second parent line

Minor Assent


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Case Report Forms (CRF)

Records and Reports

The investigator should ensure the accuracy,

completeness, legibility and timeliness of the datareported to the sponsor in the CRFs and in all

required reports.

Data reported on the CRF, which are derived from

source documents, should be consistent with the

source documents or the discrepancies should be

explained.


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Data Quality Assurance

Eligibility/Exclusion criteria

Window for visit completions

Sample tracking

Protocol compliance

Document subject study enrollment in clinicchart


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Data Quality tips

Visit window

Missed visit/incomplete visit forms

Adverse Events/Serious Adverse events

Protocol deviations

HIPAA


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Notebook #1

All HRPO submitted and approved forms

Amendments/correspondence

Recruitment materials

HRPO approved Case Report

forms/questionnaires


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Notebook #2

Manual of Operations (MOP)

Complete detailed protocol

Very detailed regarding each study

procedure


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Notebook #3

HRPO approved protocol Arbitrary how detailed you want to be

HRPO approved consents Screening Log

Lab CLIA, CAP certification, lab normals

Adverse event reports

Serious Adverse event reports HRPO requirements

Establish no bias in study recruitment


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Purpose of Audits

Verify adherence to regulatory requirements forthe protection of human subjects

Review compliance with protocol requirements

Check the accuracy of submitted data versussource documents and medical records

Learning experience for staff and Investigator


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Summary

Staff/subject relationship important to study

success

Keep the PI involved

Keep a paper trail of all correspondences

how to set up a clinical network group

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