SYDNEY MEDICAL SCHOOL

Experiences in Clinical Trials:The Good, the Bad and the Ugly

Janette Vardy

Concord Cancer Centre

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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

Dr. Haryana Dhillon – Behavioural scientistResearch co-ordinator running CRC-cognitive study Research partnersEstablished 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 ClarkeMPRU CeMPeDPsycho-Oncology Co-operative Group (PoCOG) and tumour site specific groups

Importance of the Team and Collaboration:

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The Bad

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

Many times – ready to go back to North America

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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 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

Recruitment:

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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

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

Dex Study

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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