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Experiences in Clinical Trials:
The Good, the Bad and the Ugly
SYDNEY MEDICAL SCHOOL
Janette Vardy
Concord Cancer Centre
Background
Medical Oncology -Sydney Cancer Centre
- Busy clinical commitments
- Research meetings: chemotherapy trials, basic science,
PhD (Clin Epi) and Clinical Fellowship
Prof Ian Tannock Princess Margaret Hospital – Toronto
- Clinical Epidemiology – U of Toronto
- Mentoring
- Strong research culture, infrastructure, biostatisticians, data managers, trials staff
- Protected research time
- Projects: Cognitive function & fatigue in cancer patients: CRC, Breast Cancer
Dexamethasone –for delayed emetic control
Acetaminophen/paracetamol – with strong opioids
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Research vs Clinical?
Sydney or Toronto? QOL Research or my QOL?
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Sydney or Toronto?
Cancer Institute NSW Clinical Research Fellowship -2 X 3 years
“My primary career objective is to be a successful clinician researcher,
enabling me to combine clinical research in psycho-social oncology and
survivorship with a practice in clinical medical oncology. ……
The major focus of this research programme will be cognitive function and
fatigue, and its underlying mechanisms ….
I plan subsequently to extend the research programme to address other
needs and concerns of cancer survivors, particularly targeting the
psychosocial issues that many survivors face after treatment.
Within 5 years I expect to establish a comprehensive clinical research and
clinical practice specialising in survivorship issues..”
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Back to Sydney
January 2007: Welcome Home!
Cancer Institute NSW – wage (70/30%) and $100K p.a. for research
NHMRC Grant – CRC Cognitive Study
Reality: Shared desk, no computer, most of dept on holiday
Hospital –bureaucracy:
- Having to deal with finance dept/HR/admin
- Employing staff – 6 months to employ an RA from grant
- Invited speaker at AACR/ASCO –TESL leave refused – pro-rata -days
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The Good
Importance of the Team and Collaboration:
Dr. Haryana Dhillon – Behavioural scientist
Research co-ordinator running CRC-cognitive study
 Research partners
Established and co-lead Survivorship Research Group - SuRG
>$10m in grants
6.4 FTE “ The Team” - Critical to success
Post grad and grad students: 5 PhD, 1 Masters
Psychology and Medical Student Electives, RMO projects
Writing up largest comprehensive cognitive study in cancer patients
Collaborators : neuropsychology, oncology, imaging, animal models
Local, National, International
Mentors: Ian Tannock, Martin Tattersall, Stephen Clarke
MPRU  CeMPeD
Psycho-Oncology Co-operative Group (PoCOG) and tumour site specific
groups
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The Bad
Many times – ready to go back to North America
Research Culture:
Lack of research infra-structure
Lack of protected research time for others
Lack of appreciation for investigator initiated studies and psycho-oncology
Lack of support for each others studies
Lack of support for junior staff
Give it 2-3 years: Can I change things, and if not can I live with it?
Attempted to improve research culture and build research capacity
Organised a research retreat –medical oncologists
Regular research meetings for fellows – supportive environment
Became a Clinical Academic – employed through university
More academic freedom, financial disincentives/no TESL
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The Bad
Funding: time writing grants instead of doing studies
NHMRC: inexperienced / “too junior”, not enough grants
 $2.5m CHALLENGE – Physical activity in Colon Cancer patients
21 sites across Australia
Collaboration with NCIC
Difficult / uncertain career as researcher:
Year to year funding – affect on staff and pressure on researcher
Your own job and others are reliant on you getting grants
Dec 2012 – for first time had project grants for most of our studies and
were able to keep on all our staff, but no guaranteed funding for wages
for Haryana or myself
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The Bad
Recruitment:
Recruitment to clinical studies remains a major issue
Psycho-oncology / supportive care studies –not seen as essential as
chemotherapy treatment trials or treatment affecting survival
Often difficult to get access to patients:
Lack of sponsorship  low budget – lack of reimbursement for centres
Doctors – act as “gatekeepers”
- what’s in it for me?
Lot of time/money wasted opening sites that then don’t recruit patients
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The Really Ugly
“A randomized double-blind placebo controlled cross-over trial of the
impact on quality of life of continuing dexamethasone beyond 24
hours following adjuvant chemotherapy for breast cancer”
Dual endpoints: Patient preference for one cycle over other
Change in QOL D1 – D8 –comparing 2 cycles
In house funding – 2 hospitals
Detailed protocol
n= 100 (50/group)
Experienced Trials nurse
Start up meetings
Regular progress meetings
Reviewed 1st cycle data
Analyse data for abstract preparation
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The Really Ugly
Dex Study
Review data – missing Cycle 2 Day 8 data: Patient Preference, QOL data
Nurse – hadn’t collected data
Review source documents:
Poor record keeping
Duplication of study numbers
Blood tubes – incorrectly labelled
Missing test results and questionnaires
Major International Study – same nurse was involved in
– Monitor expressed concerns re data inaccuracies – data not to be used.
PMH – Put on Hold Every Study in Breast Cancer
Review and Formal Audit
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Gets even uglier….
Outcomes:
Audits of all studies –problems were isolated to studies she was involved in
Nurse was dismissed - multiple problems across a number of her studies
Despite weekly meetings, supervision and verbal reassurances from
experienced nurse about data and study progress  PI (supervisor) ultimately
responsible for oversight of the study
Importance of checking source data
Extremely stressful for all concerned
Me – lost 3 years of work
Dexamethasone Study:
In end, only used data from other hospital  repeated the study
5 years later – finished and published.
-in meantime aprepitant became mainstream so study less topical
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Would I do it again?
Still have a passion for research in psycho-oncology/supportive
care/survivorship issues
but envious of research cultures and facilities at large North American
facilities
Now we have infrastructure and grants for our studies, it has got easier
SuRG – well trained team
 increased grants
 expanded our research programme
Funding opportunities in Australia, particularly for cancer, have improved
Research culture is growing
Increased focus on QOL/psycho-oncology studies & better quality trials in
this area
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For other researchers
Early researchers –make use of concept and protocol workshops
Get support from co-operative trials groups
Find a mentor
Build and retain a strong committed team
Mentoring and training for your staff
 do good quality trials to obtain high quality evidence
using same rigour as applied to drug trials
 apply the evidence to clinical practice
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