Transcript a comparison of long-acting injectable medications

A COMPARISON OF LONG-ACTING
INJECTABLE MEDICATIONS FOR
SCHIZOPHRENIA (ACLAIMS)
Coordinators Follow-Up and Final
Visits Procedures Review
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Welcome & Introductions
• Project Administrator—Columbia University
-Alejandrina (Alex) Estevez
• Data Coordinating Center—UNC Biostatistics
-Project Management-Tania Wilkins
-SAE/Endpoints Coordinator-Monica Miles
-Clinical Monitor-Dianne Mattingly
-Unblinded Statistician-Neepa Ray
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SPECIFIC AIMS
To compare the effectiveness, cost and tolerability of
long-term treatment with haloperidol decanoate
(HD) vs. paliperidone palmitate (PP) in patients with
schizophrenia and schizoaffective disorder:
1. therapeutic effectiveness (as measured by time
to efficacy failure)
2. cost-effectiveness over 24 months
3. incidence and severity of adverse events
4. enduring acceptability (as measured by time to
all-cause treatment discontinuation)
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TRIAL OVERVIEW
• 311/360 randomized participants with
schizophrenia or schizoaffective disorder
• 22 sites in the US
• Up to 24 months of treatment with LAI
• Participants, treating clinicians, and raters are
blinded to treatment assignment
• 15-month recruitment period
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ACLAIMS SITES
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TODAY’S REVIEW
• Primary Outcome Endpoint Monitoring and
Reporting
• Safety Monitoring and SAE Reporting
• Final Study procedures:
– Early RTDs
Psychiatric Hospitalizations
Lost to Follow-Up
--Study Assignment Completion
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TODAY’S REVIEW Cont.
• DMS Reports
– Follow-up Report
– Expected and Keyed Forms Report
– Safety Alerts
– Queries
• DMS
• Statistical
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Primary Outcome Endpoint
• Efficacy Failure reflecting inadequate
therapeutic benefit is the primary outcome
measure
• An Endpoints Adjudication Committee reviews
outcomes of each study participant and makes
the final determination
• Site clinicians provide the narrative detail
needed for these deliberations
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PRIMARY OUTCOME: EFFICACY FAILURE
Efficacy failure defined as any of the following:
• Psychiatric hospitalization
• Need for crisis stabilization
• Clinician decision to discontinue assigned LAI
due to inadequate therapeutic benefit
• Need for adjunctive oral antipsychotic
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OUTCOMES ADJUDICATION
COMMITTEE
• Panel of 3 research psychiatrists, independent
of research team and blinded to treatment
• Deliberations based largely on service use,
concomitant medications, and reasons for
study discontinuation
• Event Narrative Form (ENF) is critical to
endpoint classification process
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DATA COLLECTION FORMS/TRIGGERS
RELATED TO ENDPOINTS
• Reason for Assigned Treatment
Discontinuation Form (RTD)
• Service Utilization and Resources Form for
Monthly Items (SRF)
• Adjunctive Medication Form (AMR)
• Serious Adverse Events Form (SAE)
• Adverse Events Form (AES)
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ENF Event Triggers
• All SAEs require an ENF
• All psychiatric Emergency Room visits
-unless the ER visit is directly associated
with an SAE
• All early RTDs
-unless the RTD is directly associated with
an SAE
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ENF Triggers Cont.
What other events do not trigger an ENF?
• Non-Psychiatric Emergency Room Visits
-Site PI may determine that an ENF is not
necessary to document a potential endpoint if:
-medical in nature (i.e. sprained ankle, flu,
etc.)
-at a time when there are no psychiatric
symptoms exhibited
-the medical condition did not in any way
instigate psychiatric symptoms
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ENF Triggers Cont.
• Early Reason For Treatment Discontinuations
(RTD)
-after a psychiatric hospitalization
-participant no longer willing to take study
medication
-participant lost to follow-up for > 90 days
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EARLY RTDs
• After a psychiatric hospitalization
-every effort must be made to complete all
assessments normally conducted at the last
study visit
-Record as the visit at which the study physician
discontinued the study medication
visit number will be the same as
corresponding SAE
-Date assigned study treatment stopped?
this is the date the decision to discontinue
treatment is made
RTD form and QxQ
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EARLY RTDs
• Participant no longer willing to take study medication, but agrees to
continue follow-up visits
-every effort must be made to complete all assessments
normally conducted at the last study visit
-Record as the visit at which the study physician discontinued the
study medication
-Date assigned study treatment stopped?
this is the date the decision to discontinue
treatment is made
• If the participant later decides to withdraw from the follow-up visits, the
FWF is the only final form needed.
RTD form and QxQ
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EARLY RTDs
• Participant Lost to Follow-Up > 90 days
– RTD and FWF forms required
-Record the visit number as the visit following the last visit by
the participant while still on study medication
-Date study treatment stopped 90 days after the last
injection if no other information is available
– ENF is required
• if possible, note signs and symptoms relating to lost to follow-up
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QUESTIONS?
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SAFETY MONITORING
DSMB Safety Action Plan
• Central oversight of all clinically significant laboratory
values
• Post-baseline lab values that are clinically significant
will be flagged for review and discussion between
the site PI and the project Safety Officer to
determine an appropriate plan, which may include
discontinuation of study treatment
• Prolactin-related monitoring in place
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LABORATORY TEST ASSESSMENTS
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Hematology
Serum chemistries
Fasting lipids
Fasting blood glucose and insulin levels
Urine screen for drugs of abuse
Prolactin
Serum pregnancy test for women who can
become pregnant
• Additional WBC’s when indicated
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SAFETY ALERTS
• Additional safety situations that warrant consultation with the
Safety Officer
- Hospitalization for any reason
-Worsening tardive dyskinesia
-Weight gain of 15 pounds or more
-An increase in LDL cholesterol of 20mg/dL
-New onset diabetes mellitus (FBS > 200)
-significant clinical worsening as indicated by CGI score
DMS has a Safety Alert Report for monitoring these situations
Protocol v7.6 Section 7.2.10
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ACLAIMS SAFETY OFFICER
• Tom Smith, MD, Columbia University
• Will review all SAEs to make sure they have
information required by DSMB
• If needed, will communicate with site physician to
make specific requests
• To be consulted in adverse safety situations about
appropriateness for continuation on study medication
if there is a desire to continue the medicine
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PROJECT MEDICAL OFFICERS
• Drs. McEvoy and Byerly
• Address clinical and medication management
questions
• Develop laboratory monitoring plan for
participants who have a history of leukopenia/
develop leukopenia during trial
• Address protocol questions and violations
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SERIOUSADVERSE EVENTS
A serious AE is defined as one that satisfies any
of the following criteria:
• Results in Death
• Is immediately life-threatening, including
potentially life threatening suicidal behavior
that results in hospitalization
Any fatal or life threatening AE’s must be
reported immediately
Protocol v7.6, Section 5.1.1-4
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SERIOUS ADVERSE EVENTS—cont.
• A serious AE is defined as one that satisfies any on
the following criteria:
• Requires inpatient hospitalization or prolongation of
existing hospitalization
• Results in persistent or significant disability or
incapacity
• Is a congenital abnormality or birth defect
• Is an important medical event that may jeopardize
the subject or may require medical intervention to
prevent one of the outcomes listed above.
Protocol v7.6, Section 5.1.1-4
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SERIOUS ADVERSE EVENTS
• Per NIH guidelines:
The trial period is defined from the time
that the informed consent document is signed
until 30 days after study withdrawal.
Participants continuing in follow-up visits
after early discontinuation from study drug must
be monitored for SAEs and all SAEs reported.
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SAE Procedures
• All SAEs must be initially reported to the DCC within 24
hours after a site becomes aware of an occurrence.
• Please note that an SAE is not considered reported
until entered into the DMS.
• Sites must report SAEs that are unanticipated and
related to FDA within 10 days. (We will assist.)
• Some site IRBs may require reporting of other adverse
events or experiences that do not fit the description
above. This additional reporting is the site’s
responsibility (as is all IRB reporting), and is not part of
study data collection.
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Required SAE Information
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Timing of SAE
Primary diagnosis/description of event
Diagnostic procedures (if any)
Relationship according to the investigator
Action taken for the SAE, e.g., stopping the drug, etc.
Outcome of SAE
Other Adverse Events: Only AEs related to the SAE
should be mentioned.
• Laboratory findings and Vital signs: Only those that are
related to the SAE should be provided.
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Steps for SAE Reporting
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Complete the SAE form with as much information as possible, following
the instructions in SRM Chapter 8. The PI or study physician should sign
all completed SAE forms.
Assign the appropriate visit# and seq#. For the initial report, use SEQ
number 101. For any later updates to the form for this SAE, use SEQ 102,
103 and so on. If a different SAE occurs on a participant at the same visit
number, that Seq # series then begins with 201…
Key the form into the DMS.
Call the DCC Help Line 1-866-659-3064 to notify them of an SAE.
The DCC and/or Alex will review the data and send out queries if needed.
The DCC will notify and report the SAE to the Safety Officer.
The Safety Officer may request additional information on the Event
Any follow-up information that updates this event must be recorded on a
new SAE form that is documented as follow-up with the next Seq #
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DO NOT include in SAE reports:
• Any identifying information, e.g.:
– Patient's name or initials
– Anything indicating geographic location or
research site (such as names of hospitals or
facilities, names of clinicians or study coordinators
or any other identifiers)
– Do not include participant study ID in note-log
narrative
– Place a participant ID label on paper copy
narrative
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QUESTIONS?
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NARRATIVES—SAE & ENF
• What’s the difference?
– SAE narratives are needed to help IRBs and the DSMB
understand the safety of the study treatments and
procedures—the relationship between the SAE and the
study medication is critical
– ENF narratives are necessary to help our Adjudication
Committee determine if an efficacy failure has occurred
and thus require more information about symptoms and
behaviors
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ENF NARRATIVE GUIDELINE
The following information about any event signifying a possible
efficacy failure should always be provided:
– Timing of Event
– Description of Event including symptoms and behaviors
– Circumstances surrounding event
– Action taken (e.g., used oral medication, stopped LAI, none needed)
– Outcome of event or relevant subsequent events
Avoid Personal Health Information (PHI)/any identifying information
Make sure dates in narrative correspond with dates on other forms
Use the Clinician’s Check List on the ENF form to guide the narrative
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NARRATIVES—SAE & ENF
• Create all narratives in a word document and
copy and paste into the note-log item.
-ENF form: Item 4
-SAE form: Item 14
• The paper form is considered a source document:
a study ID label should be placed and the
narrative filed with the paper CRF
• Simple corrections to paper note-logs may be
done with a single-line cross through, initials and
date
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NARRATIVES cont.
• Copy and paste the contents of the document
into the DMS note-log by:
-Open the narrative document and select “select all” from the Edit
menu on the Windows Tool Bar. Then select “copy” from same
menu
-Minimize the document and then open the note-log for copying
-Use the key combination “SHIFT + INSERT” to paste the document in
the note-log
-Save the note-log by using the key commands “ALT + S”
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NOTE-LOG PROBLEM
• What’s the problem?
– The problem is that a user sometimes can’t save a changed form
– The problem stems from an apostrophe (‘) or quote (“) copied from
WORD and saved in a note-log from a previous session.
– The DMS converts to boxes ( □ )
Note: the apostrophe or quote will look normal at first. It will only have
the box look after the form has been saved and re-opened
• What’s the solution?
- The user can leave apostrophes/quotes out. After copying into the
DMS add the apostrophes/quotes
- The user can correct boxes as required.
Note: The initial form will save with no problem. The problem only
occurs when trying to change a previously saved form
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QUESTIONS?
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DMS REPORTS AND QUERIES
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Statistical Queries
• Statistical Queries are queries that are generated
by our statisticians based upon a data retrieval
• Statistical Queries are not generated by the DMS
and not resolved through DMS query resolution
• To resolve—click on remote data entry from the
main DMS menu and select the participant, visit
and form.
• Open the form, resolve the query and Select save
the form from the CHANGES menu
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