Monitoring PaCCSC studies
Improving quality
Flinders University receives funding for
PaCCSC from the Australian Government
Department of Health and Ageing under the
National Palliative Care Program.
Acknowledgements

Each and every site
– Investigators
– Site coordinators
– Study staff

Caroline Litster, Natalie Cutri, Linda
Devilee
Brief overview

PaCCSC has a comprehensive
monitoring programme
– Unusual for investigator initiated studies
– Usual for pharmaceutical sponsored studies
– Programme is based on best practice and
ICH GCP guidelines
• All sites
• All participants
– Incorporates an element of pragmatism and
realistic opportunity
Monitoring


GCP requirement of sponsors
Verifies
– rights and well being of participants
– protocol has been followed
– trial conduct is in compliance with GCP

Also a means to verify participant data
– Data used in the study analysis is correct and can
be verified from other sources
– The study results are based on the data from
participants
– ensures that participant data counts
Monitoring

Is a detailed review of study documents,
protocol implementation and procedures
– After study is complete this is the only way to
verify compliance


Enables assessment of each site and the
opportunity to provide support for specific
problems
Enables training at each site to bring
about internal quality improvement
Monitoring



Assess all site files
Review all participant files against source
documents
Targeted review of critical data elements
–
–
–
–
–
–
Eligibility
Consent
Administration of study medication
Review of safety assessments
Review of primary outcome assessments
Reasons for cessation
What worked well

Early monitoring included a variety of
strategies
– Aimed at simply getting through the numbers
of files required
– Also to increase learning amongst sites and to
increase the capacity of all in a period of
learning and expansion
– Fostered mentoring between recruitment sites
and with PaCCSC
Ketamine study



Monitoring included taking a site
coordinator to monitor another site along
side the PaCCSC monitor
Rotated at least once
On site training
Ketamine study



Enabled each site coordinator to see
how another site organised their files,
how they prepared for monitoring, and
what problems arose
Site coordinators could discuss
recruitment, filing, organisation and
staffing issues
Good feedback, and some sites
implemented some of the tips seen at the
other site
Ketamine study


Did this process bring about
improvements in basic monitoring
outcomes for this or future studies
The main problems for this study
– First study and everyone was learning
– Changes in HREC organisation occurred
Octreotide study

Impending study closure initiated a
different monitoring strategy
– All study nurses joined a teleconference to
review and discuss the specific monitoring
needs for this study
– Details of monitoring process, paperwork and
assessment was discussed
– Each study nurse then monitored another site
alongside a PaCCSC monitor
Octreotide study


Study nurses could see for themselves
what was monitored, how files at other
sites looked, and what problems were
found
Provided an opportunity to prepare their
own files for subsequent monitoring.
Octreotide study


Did this process bring about
improvements in basic monitoring
outcomes for this or future studies
The main problems for this study
– Study was nearing completion and findings
could not be implemented at sites for
subsequent participants
Risperidone study

Specific issues related to consent and
medication dosing
 Monitoring has been later than other
studies so lessons learned from earlier
should be seen here
What didn’t work well

Organisational factors
– Very difficult to arrange dates and sites
availability
• PaCCSC monitors
• Site to be monitored
• Site providing support monitor

Personnel factors
– Much time taken up with training on site,
slows down the process
– In some cases, networking, discussion and
learning resulted in slow file review.
Results


Did any of these activities result in
improvement in monitoring outcomes at
sites?
Three studies were examined
– Ketamine, inpatient study, complete
– Octreotide, inpatient study, complete
– Risperidone, inpatient study, almost complete
General methods

Reviewed all the corrective action sheets
– Listed the number of actions for each
participant at each visit, along with date of
randomisation
– Listed the number of actions related to
general site investigator files
– Noted the dates of any training (during
ketamine, octreotide, or due to previous
monitoring)
– Determined the average number of errors for
before training and after training.
Results
Only 1 participant prior to
training
Ketamine study
Only 1 participant after
training
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
A
B
C
D
Average errors prior to training
E
F
G
H
Average errors post any training
I
Results
Octreotide study
7.00
6.00
Only 1 participant prior to
training
Did not have
training
5.00
4.00
3.00
2.00
1.00
0.00
A
B
C
D
E
F
Average errors prior to training
G
H
I
J
K
Average errors post any training
L
Results
Risperidone study
4.5
No errors in early
monitoring
4.0
Only 1 participant after
training
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
A
B
C
D
E
Average errors prior to training
F
G
H
I
Average errors post any training
J
Next time

Reinforce that monitoring is a QA activity
– Results from one visit should be corrected:
• For the reviewed file
• For next files and future files
• For monitored study and other studies

Recognise that sites value visits to other
sites
– to compare notes and see what they are
doing
– How can we continue to learn and share
experiences
Next time

There are common errors across all
studies, and errors specific to a particular
study
– We need to identify the common errors and
determine ways to improve
• Consent
– Signing, filing, documentation
• Documentation
• Completion of the CRFs
– Answer every question
• Ensuring that source documents are clear and
available
Next time

Each site needs to discuss the
monitoring outcomes between
themselves
– Look at the corrective actions
– How could this have been avoided
– What can be improved for next time and not
repeat the same errors

What can PaCCSC do to assist?