research investment evaluation 2011-2012

1

Research Investment Evaluation 2011-2012

i

Table of Contents

List of Tables and Figures……………………………………………………………………………………………………ii

Executive Summary………………………………………………………………………………………………………….iv

CCNSW Research Portfolio

Research Investment……………………………………………………………………………………………………..2

Research Investment by Funding Scheme…………………………………………………………………………….3

Research Investment by Administering Institution…………………………………………………………….………6

Research Investment by cancer type…………………………………………………………………………………..8

Strategic Research Investment at Cancer Council NSW…………………………………………………………….9

Success rates for Cancer Council NSW funding applications…………………………………………..…….……10

Key Performance Indicators

Monitoring and Evaluating Research………………………………………………………………………………….13

KPI 1: Measuring the level of funding and sustainability of Cancer Council NSW research……………………14

1.1 Maintain position as largest non-government funder of cancer research in NSW……………………14 1.2 Maintain current level of funding allocated to cancer research…………………………………………14 1.3 Funding leveraged against CCNSW research investment……………………………………………...16

KPI 2: Measuring the linkages and connection between research and practice…………………………………16

2.1 Evidence of research procurement towards the application of research…………………….…………16 2.2 Evidence of research involving consumers…………………………………………………….………….18 2.3 Evidence of supporting multidisciplinary research teams…………………………………….………….19

KPI 3: Measuring the quality, success and influence of research……………………………………………....…21

3.1 Evidence of productivity and contribution to knowledge and evidences……………………………….21 3.2 Evidence of influence on knowledge and evidence……………………………….……………………...21

KPI 4: Measuring transparency………………………………………………………………………………………..24

Research Outcomes: Case Studies

STREP Grant case study: Progression of Barrett’s Esophagus to Cancer Network (PROBE-NET)……….….27

Project Grant case study: Functional characterisation of the putative tumour suppressor gene MCC in colorectal cancer……………………………………………………………………………………………………..….32

Program Grant case study: Building capacity in pharmacogenomics across NSW: PRIMe (Pharmacogenomic Research for Individualised Medicine)………………………………………………………………………….…….34

Appendices

Appendix 1: List of grants awarded 2011-2012………………...……………………………………………………37

Appendix 2: Common Scientific Outline………………………………………………………………………………40

ii

List of Tables

Table 1: Cancer Council NSW new external research funding commitments, 2006-12 .................................. 2 Table 2: 2011 new external research funding commitments by Administering Institution ............................... 6 Table 3: 2012 new external research funding commitments by Administering Institution ............................... 6 Table 4: 2011 and 2012 new external research funding commitments by Administering Institution ............... 7 Table 5: Success rates for applications to CCNSW funding schemes (2011 and 2012) .............................. 11 Table 6: Consumer participation in reviewing grant applications 2011 and 2012 (KPI 2.2) .......................... 18

Table 7: Publications for grants that ended in 2011 and 2012 by CCNSW funding scheme (KPI 3.1) ......... 21 Table 8: Impact factors for publications arising from grants that completed in 2011 and 2012, by CSO ...... 22 Table 9: Citations for grants that completed in 2011 and 2012, by CSO (KPI 3.2) ....................................... 23 Table 10: PRIMe studies and recruitment as at June 30 ................................................................................ 35

List of Figures

Figure 1: 2011 new external research funding commitments, by funding program .......................................... 5 Figure 2: CCNSW new external research funding commitments 2011 and 2012, by jurisdiction .................... 7

Figure 3: CCNSW 2011 and 2012 new external research funding commitments by cancer type (%) ............. 8 Figure 4: CCNSW 2011 and 2012 external research expenditure: priority-driven versus investigator-initiated

research ............................................................................................................................................ 9 Figure 5: External research expenditure in CCNSW strategic priority areas 2006-2012, with percentage of

overall research expenditure in each year ...................................................................................... 10

Figure 6: Cancer Council NSW funding position 2011 and 2012 (KPI 1.1) .................................................... 14 Figure 7: CCNSW expenditure 2011 and 2012, with percentage of research expenditure (KPI 1.2) ............. 15 Figure 8: CCNSW expenditure 2006-2012, with percentage of external research expenditure ..................... 15 Figure 9: Distribution of CCNSW External Research funding awarded in 2011 and 2012 across Common

Scientific Outline categories, compared against all cancer research conducted in Australia and NSW in 2003-2005 (KPI 2.1) .......................................................................................................... 17

Figure 10: Distribution of CCNSW External Research funding awarded in 2011 and 2012 across Common Scientific Outline classifications ...................................................................................................... 17

Figure 11: Number of Chief Investigators per grant funded in 2011 and 2012, by funding scheme ................ 19 Figure 12: Number of institutions per grant funded 2011 and 2012, by funding scheme ................................. 20 Figure 13: Citation tree for Nancarrow DJ, Handoko HY, Smithers BM, Gotley DC, Drew PA, Watson DI,

Clouston AD, Hayward NK & Whiteman DC. Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High- Density Single-Nucleotide Polymorphism Arrays, Cancer Research (2008) 68:4163-4172. ..................................................................................................................... 30

iv

Executive Summary

Cancer Council NSW Research Portfolio

• Cancer Council NSW (CCNSW) is the largest non-government funder of cancer research in Australia.

• Since 2006, CCNSW has committed more than $61 million in new funding to the External Research Program. During 2011 and 2012, CCNSW committed close to $22 million in new funding to the External Research Program.

• CCNSW supports the External Research Program through five main competitive funding programs: Project, Priority-driven Collaborative Cancer Research Scheme, Program, Strategic Research Partnership, and Innovator Grants.

• The majority of external research funding committed in 2011 was to support four new Program Grants, while 100% of external funding committed in 2012 was for 11 new project grants.

• Between them, the University of New South Wales and the University of Sydney were

awarded just over half of all new external research funding committed by CCNSW during 2011 and 2012.

• Of external research funding committed by CCNSW during 2011 and 2012, just over $20

million (96.2% of total new funding) was awarded to researchers located in NSW. • During 2011 and 2012, the CCNSW External Research Program invested most heavily in

brain, leukaemia, breast, pancreatic, and colorectal cancers.

• 77.3% of 2011 and 2012 external research expenditure was awarded to investigator-initiated research, with 22.7% awarded to priority-driven research.

• CCNSW strategic priorities are pancreatic, oesophageal, colorectal, and brain cancers,

and behavioural and psychosocial issues in cancer control. CCNSW investment in these strategic priorities increased substantially during the period 2006-2012, rising from 30% of overall research expenditure in 2007 to 60% of overall research expenditure in 2012.


The CCNSW External Research Program reports against four Key Performance Indicators (KPIs; see p.13 for a full list):

1. Measuring the level of funding and sustainability of CCNSW research

• CCNSW is the third largest cancer research funder in NSW, behind two government funded agencies, which make CCNSW the largest non-government funder of cancer research in Australia.

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• During 2011 and 2012, total CCNSW research expenditure remained at around 30% of overall CCNSW expenditure. Investment in the External Research Program alone accounted for 19.3% of overall organisational expenditure in 2011; and 16.3% in 2012.

• CCNSW made an initial investment of $12.1 million in external research projects that were completed in 2011 and 2012, which went on to leverage a further $27.6 million. In other words, for every dollar CCNSW invested in those grants, the research teams raised a further $2.28 to continue their research and ensure the sustainability of research momentum.

2. Measuring the linkages and connections between research and practice

• Reflecting the broader Australian cancer research landscape, the highest proportion of CCNSW external research funding committed during 2011 and 2012 was to support research classified under the Common Scientific Outline (CSO) as biological research (34.5%), followed by treatment (26.5%)

• Just over half of external research funding (50.9%) committed during 2011 and 2012 was distributed towards the application of research, namely the CSO categories of Early Detection, Diagnosis, and Prognosis; Treatment; Cancer Control, Survivorship, and Outcomes; and Scientific Models Systems.

• Consistent with the different foci of the CCNSW external research funding schemes, the distribution of CCNSW external research funding across the Common Scientific Outline categories differs across the various funding schemes.

• During 2011 and 2012, 138 funding applications were reviewed by consumers.

• Thirty-three percent of projects awarded more than $300,000 per year in external research funding during 2011 and 2012 were led by multidisciplinary research teams.

3. Measuring the quality, success and influence of research

• Among external research projects that were completed in 2011 and 2012, the mean number of publications was 4.5 for Project Grants, 40 for STREP Grants, and 1.5 for Innovator Grants.

• Among external research projects that were completed in 2011 and 2012, teams funded to conduct research in the CSO classification areas of Biology, Aetiology, Prevention, Early Detection, Diagnosis, and Prognosis, and Treatment published their results in journals with higher average impact factors than research teams funded to conduct research in the CSO classification areas of Cancer Control, Survivorship, and Outcomes, and Scientific Model Systems.

• Among external research projects that were completed in 2011 and 2012, the percentage of publications that met expected citation (average number of citations to articles of the same document type from the same journal in the same database year) at year one ranged from 50% for those funded under the CSO classification of Scientific Model Systems, to 65.7% for the CSO classification of Early Detection, Diagnosis, and Prognosis.

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4. Measuring transparency

• During 2011 and 2012, the CCNSW External Research Program met all KPIs (see p.22 for a full list), with the exception of KPI 2.1, which has the aim that 100% of teams funded at more than $300,000 per year are multidisciplinary.

Research Outcomes: Case Studies

To highlight the outcomes of research funded through the CCNSW External Funding Program, three cases studies are provided:

• STREP Grant case study: Progression of Barrett’s Esophagus to Cancer Network (PROBE-NET);

• Project Grant case study: Functional characterisation of the putative tumour suppressor gene MCC in colorectal cancer; and

• Program Grant case study: Building capacity in pharmacogenomics across NSW: PRIMe (Pharmacogenomic Research for Individualised Medicine)

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CCNSW Research Portfolio

2

Research Investment

Cancer Council NSW (CCNSW) is the largest non-government funder of cancer research in Australia. CCNSW’s current research strategy focuses on funding world-class, ground-breaking research to cover all aspects of cancer control. The organisation’s first strategic priority is to drive major advances in research and to ensure no cancer is ignored. CCNSW research is broadly structured into two programs, the Internal and External Programs. The Internal Research program is conducted by researchers located within CCNSW. CCNSW’s Cancer Research Division investigates the causes, management, outcomes and impact of the leading and emerging cancers. The Division’s two main focus areas are epidemiological population studies into cancer causes and risks; and health services research and patterns of care studies. CCNSW’s Health Strategies Division undertakes strategic research to inform the development of prevention programs, policy positions and advocacy campaigns, and to evaluate their outcomes. CCNSW’s Cancer Information and Support Services Division undertakes research into the psychosocial aspects of cancer care. CCNSW’s External Research Program supports the work of researchers located in institutions outside of CCNSW. It is the External Research Program which is the subject of this Research Investment Evaluation Report 2011-2012. As a community-funded organisation, the funds available to support CCNSW’s External Research Program depend on the donations of our supporters. CCNSW therefore strives to fund research that is not only of the highest scientific merit, but is also of value to the community who support us. Since 2006, CCNSW has committed more than $61 million in new funding to the External Research Program (Table 1).1 Table 1: Cancer Council NSW new external research funding commitments, 2006-12

Year New funding committed

2012 $3,959,700

2011 $17,941,023

2010 $6,781,493

2009 $5,563,082

2008 $8,750,794

2007 $4,860,784

2006 $13,467,258

Total 2006-2012 $61,324,134

1 New funding refers to new grants commencing in a given year. Research expenditure refers to payments in a given year to grants that have commenced in a previous years.

3

Research Investment by Funding Scheme

CCNSW supports research through five main competitive funding programs.

Project Grants

Awarded every year, CCNSW Project Grants fund discrete, investigator-initiated projects into all aspects of cancer, including its causes, mechanisms, prevention, treatment and care, and the organisation and performance of cancer control services.

Project Grant applications are subject to scientific peer review and ranking through the National Health and Medical Research Council (NHMRC) Project Grant process. In addition, applicants for CCNSW Project Grant funding must address five criteria of specific relevance to cancer consumers (patients, carers and survivors). All applications deemed fundable by the NHMRC are subsequently reviewed and ranked by a panel of consumers trained in the assessment of funding applications. The NHMRC scientific review scores and the scores assigned by the Consumer Review Panel are combined to derive final rankings of applications, on which subsequent funding decisions are based.

Maximum funding amount: $360,000

Maximum funding term: 3 years

Priority-driven Collaborative Cancer Research Scheme (PdCCRS)

CCNSW is a funding partner in Cancer Australia’s Priority-driven Collaborative Cancer Research Scheme (PdCCRS). Each funding partner has the opportunity to set a research priority, which must be addressed by applications for their PdCCRS funding. Like CCNSW Project Grants, applications to the PdCCRS are subject to scientific peer review through the NHMRC, and are subsequently subjected to an additional level of review administered by Cancer Australia. Cancer Australia’s criteria address collaboration, consumer involvement, and clear translational pathways to improve cancer outcomes.

PdCCRS Grants funded by CCNSW are selected according to their scientific merit and their alignment with CCNSW research priorities. They are administered as Project Grants at CCNSW, and their outcomes are classified with Project Grants data in this report.



Program Grants

Program Grants support broad-based, collaborative research by large, multidisciplinary teams with outstanding track records. They are designed to provide longer-term funding security to such teams to enhance their productivity and support a freedom and flexibility of enquiry beyond that achievable through other types of grants.

Program Grants are available for research into all aspects of cancer, including its causes, mechanisms, prevention, treatment and care, and the organisation and performance of cancer control services.

Maximum funding amount: $2,250,000


4

Strategic Research Partnership (STREP) Grants

The STREP program aims to encourage progress in underdeveloped areas by funding research with clear potential to impact cancer policy and practice. STREP funding particularly addresses cancers or populations with poor outcomes, or where funding through other mechanisms has lagged behind clinical or public health need.

STREP Grants build capacity by bringing together large teams of researchers and clinicians from a range of disciplines who can together achieve more substantial outcomes than would be possible if they all worked individually. A unique feature of the STREP program is that CCNSW becomes a partner in the research process, collaborating with these multidisciplinary research groups to accelerate the uptake of new research findings into practice or policy. The aims and activities of each of the three STREP stages are described below:

Stage 1 – Foundation stage

• The capacity of research teams to effectively undertake practice innovation and to translate research findings into the clinical or public health setting is developed, augmented, and extended

• The core research agenda is developed and implemented • Potential collaborative activities in cancer control between CCNSW, the STREP

research team and others are explored

Stage 2 – Consensus building for research prioritisation

• CCNSW undertakes an evidence-based review of science and practice • CCNSW works collaboratively with the research team, experts in the field and

cancer consumers to develop, endorse, and publish a shortlist of research questions and objectives within the area of cancer control addressed by the STREP Grant, that are:

(i) appropriate to the Australian context; and (ii) likely to produce significant improvements in outcomes or breakthroughs

important to people affected by cancer

Stage 3 – Research procurement

• CCNSW develops a research procurement strategy to address the objectives identified in Stage 2

Areas investigated by STREP teams become CCNSW research priorities. In practical terms, this translates to increased investment in the areas investigated by STREP Grants over subsequent years. This investment ensures an under-resourced area receives the necessary resources to drive major research advances to improve outcomes.

Maximum amount: $2, 000,000


5

Appendix 1 lists all projects awarded External Research program funding in 2011 and 2012. In 2011, CCNSW committed new external research funding under each of the five main competitive funding programs (Project, PdCCRS, Program, STREP and Innovator Grants). Funds were also awarded in 2011 to support the development of a Clinical Trial Protocol, and to fund the Melanoma Genome Project, deemed a strategically significant opportunity to which CCNSW should contribute. The four Program Grants awarded in 2011 constituted the majority of new funding committed that year (Figure 1). In 2012, funds were committed to 11 Project Grants, including three PdCCRS Grants.

Figure 1: 2011 new external research funding commitments, by funding program

1% 0%

3%

50% 31%

15%

Special

Clinical Trial Protocol

Innovator

Program

Project

STREP

Innovator Grants

A form of calculated risk-taking, Innovator Grants are designed to encourage researchers to enter a new field of cancer research and to explore innovative research ideas that may be challenging to fund via traditional, more conservative sources. Relative to other funding programs, the assessment of Innovator Grants focuses less on the researcher’s track record, and more on the capacity of the proposed research to facilitate novel research approaches with high potential to advance cancer control.


Maximum funding term: 1 year

6

Research Investment by Administering Institution

The Administering Institution is the institution that submits a research funding application on behalf of the applicant and subsequently administers any grant funds awarded. During the grant selection process, peer reviewers ensure that the researchers CCNSW funds have the support of an institution that receives and accounts for grant funds. The Administering Institution may not necessarily be the Institution where the research is actually conducted.

During 2011 and 2012, CCNSW committed close to $22 million in new external research funding. The largest proportions of these new external research funds were awarded to the University of New South Wales in 2011 and the University of Sydney in 2012 (Tables 2 and 3). Together, these two Institutions were awarded just over half of all new external research funding commitments made by CCNSW during 2011 and 2012 (Table 4).

Table 2: 2011 new external research funding commitments by Administering Institution

Administering Institution 2011 new funding commitments

Percentage of new funding

commitments

University of New South Wales $6,223,228 34.7%

Garvan Institute of Medical Research $3,749,976 20.9%

University of Sydney $3,142,823 17.5%

Children's Medical Research Institute $2,250,000 12.5%

University of Newcastle $1,979,044 11.0%

Melbourne Health $345,617 1.9%

University of Melbourne $100,000 0.6%

University of Adelaide $94,255 0.5%

Charles Sturt University $56,080 0.3%

Total $17,941,023 100% Table 3: 2012 new external research funding commitments by Administering Institution

Administering Institution 2012 new funding commitments


commitments


University of New South Wales $797,350 20.1%

Melanoma Institute Australia $479,428 12.1%

Garvan Institute of Medical Research $357,140 9.0%

Cancer Council Victoria $301,957 7.6%

University of Newcastle $260,000 6.6%

Total $3,959,700 100%

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Table 4: 2011 and 2012 new external research funding commitments by Administering Institution

Administering Institution 2011 and 2012 funding commitments


commitments

University of New South Wales $7,020,578 32.1%


Garvan Institute of Medical Research $4,107,116 18.8%

Children's Medical Research Institute $2,250,000 10.3%

University of Newcastle $2,239,044 10.2%

Melanoma Institute Australia $479,428 2.2%

Melbourne Health $345,617 1.6%

Cancer Council Victoria $301,957 1.4%

University of Melbourne $100,000 0.5%

University of Adelaide $94,255 0.4%

Charles Sturt University $56,080 0.3%

Total Funding Awarded in 2011 and 2012

$21,900,723 100%

CCNSW’s External Research program predominately funds researchers based in Administering Institutions located in NSW; however, the commitment to funding the best research means that funding may support researchers located in other jurisdictions. During 2011 and 2012, we committed just over $20 million in new funding to support researchers located in NSW (96.2% of total new funding commitments); $747,574 to support researchers located in Victoria (3.4%); and $94,255 to researchers located in South Australia (0.4%) (Figure 2).

Figure 2: CCNSW new external research funding commitments 2011 and 2012, by jurisdiction

$0

$5,000,000

$10,000,000

$15,000,000

$20,000,000

$25,000,000

NSW SA VIC

2012 new fundingcommitments

2011 new fundingcommitments

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Research Investment by cancer type

CCNSW aims to fund research into high-incidence and high-mortality cancers. We also aim to fund research into cancers and issues which are under-resourced – that is, where funding levels lag behind the associated burden of disease.

In 2008 (the year for which the most recent NSW cancer statistics are available), prostate, breast, melanoma, lung and colon cancers were the most common cancers diagnosed among the NSW population. In the same year, lung, colon, prostate, breast and pancreatic cancers were the most common causes of cancer death. During 2011 and 2012, the CCNSW external research program invested most heavily in brain cancer, leukaemia, and breast, pancreatic, and colorectal cancers (Figure 3).

Figure 3: CCNSW 2011 and 2012 new external research funding commitments by cancer type (%)

0 5 10 15 20

Oesophagus

Haemotological

Liver

Ovarian

Prostate

Lymphoma

Other non-specific basic science…

Bone and connective tissue

Lung

Neuroblastoma

Melanoma

Mental health and psychosocial factors

All cancers

Colorectal

Pancreas

Breast

Leukaemia

Brain

Percentage of overall external research funding

http://www.cancerinstitute.org.au/data-and-statistics/cancer-statistics/online-statistics-module

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Strategic Research Investment at Cancer Council NSW

CCNSW 2011 and 2012 research expenditure can be classified as either investigator-initiated or priority-driven.2 Calculations based on these classifications indicated that over the period 2011-2012, priority-driven research accounted for 22.7% of External Research Program expenditure (Figure 4).

Figure 4: CCNSW 2011 and 2012 external research expenditure: priority-driven versus investigator-initiated research

CCNSW strategic research investment is achieved primarily through the STREP funding program and, during the research procurement undertaken in STREP Stage 3, through Innovator Grants and PdCCRS Grants (more detail on this process is provided on page 13).

In 2006, CCNSW funded three STREPs, focussing on pancreatic cancer, colorectal cancer, and behavioural and psychosocial issues related to cancer. In 2008, another three STREPs were funded, focussing on liver cancer, brain cancer, and oesophageal cancer; followed by an additional two in 2011, in pancreatic cancer and in behavioural and psychosocial issues related to cancer.

2 The following research was classified as investigator-initiated: All Project Grants; All Program Grants except the Pharmacogenomics Research for Individualised Medicine (PRIMe) Program Grant and the ICGC: International Cancer Genome Consortium Program Grant; All Strategic Research Partnership (STREP) Grants except the Newcastle Cancer Control Collaborative (New-3C); the Melanoma Genome Project; and two small grants (a total of $59,000) awarded in 2012. The following research was classified as priority-driven: All Innovator Grants; the three Commissioned Strategic Research Grants; all Priority-driven Collaborative Cancer Research Scheme Grants, including those to which CCNSW contributes on behalf of Cancer Council Australia (and which thus contribute to Cancer Council Australia’s priorities); the one Clinical Trial Protocol Grant (funded to facilitate the development of a clinical trial protocol for treatment of Barrett’s oesophagus/oesophageal carcinoma); the Pharmacogenomics Research for Individualised Medicine (PRIMe) Program Grant; the Newcastle Cancer Control Collaborative (New-3C) Grant; the ICGC: International Cancer Genome Consortium Program Grant; and the 45 & Up Grant (Sax Institute).

22.7%

77.3%

Priority-driven research

Investigator-initiated research

10

The staged nature of STREP Grants ensures that areas funded through the STREP scheme become CCNSW research priorities, and investment in these areas increases over subsequent years. The mechanisms by which this is achieved are the Innovator Grant program, which calls specifically for research into the areas nominated as priorities during STREP Stage 2 priority-setting process; and the PdCCRS, where CCNSW nominates the priority which applications for funding must address.

Figure 5 demonstrates that CCNSW investment in pancreatic, oesophageal, liver, colorectal, and brain cancer and behavioural and psychosocial issues related to cancer increased substantially over the 2006-2012 period, from an expenditure of $1.3 million in 2006 to $4.7 million in 2012; and accounted for 60% of CCNSW’s total 2012 External Research Program expenditure.

Figure 5: External research expenditure in CCNSW strategic priority areas 2006-2012, with percentage of overall research expenditure in each year

Success rates for Cancer Council NSW funding applications

Table 5 depicts success rates for applications to each of CCNSW‘s main competitive funding programs for the years 2011 and 2012. Success rates depend on the number of applications submitted to a particular scheme and the funding allocated to that scheme in a given year.

For example, in 2011 CCNSW received 40 applications to the Project Grant scheme, and was able to fund 16 grants, which resulted in a success rate of 40%. In contrast, in 2012, CCNSW received 119 applications to the Project Grant scheme and was able to fund 12, resulting in a success rate of 10%. As the broader Australian research funding landscape becomes more competitive, it is expected that there will be an increasing number of researchers that apply to CCNSW funding schemes.

39% 30%

35%

37% 42%

55%

60%

$0

$1,000,000

$2,000,000

$3,000,000

$4,000,000

$5,000,000

$6,000,000

2006 2007 2008 2009 2010 2011 2012

Liver

Brain

Oesophagus

Colorectal

Pancreas

Psychosocial

11

Table 5: Success rates for applications to CCNSW funding schemes (2011 and 2012)

Grant Type

2011 2012

Applications Received

Number Funded

Success Rate

Applications Received

Number Funded

Success Rate

Project 40 16 40% 119 12 10%

Program 10 4 40% 0 0 0

STREP 4 2 50% 0 0 0

Innovator 36 9 25% 0 0 0

Overall 90 31 34% 119 12 10%

12


13

Monitoring and Evaluating Research

Research is one of CCNSW’s most important investments. CCNSW is committed to ensuring that the research we fund not only advances scientific knowledge, but that it also benefits the community that supports us. Measuring research outcomes is a key responsibility of CCNSW’s Research Strategy Unit, which administers the External Research Program.

CCNSW reports against Key Performance Indicators for research across four areas:

1. Level of funding sustainability of CCNSW research 1.1. CCNSW position as the largest non-government funder of cancer research in NSW

retained 1.2. Current level of funding allocated to cancer research maintained

2. Linkages and the connection between research and practice

2.1. Evidence of research procurement towards the application of research 2.2. Evidence of research involving consumers 2.3. Evidence of supporting multidisciplinary research teams

3. Quality, success and influence of the research

3.1. Evidence of productivity and contribution to knowledge and evidence 3.2. Evidence of influence on knowledge and evidence

4. Transparency

4.1. Evidence of research evaluation

The indicators were developed under the direction of the CCNSW Cancer Research Committee, a sub-committee of the CCNSW Board responsible for providing guidance on cancer research policy and programs; and were reported against in the first report in this series, the Research Investment Evaluation Report 2006-2010.

This section of the report represents the outputs of research completed during 2011 and 2012 which was funded under CCNSW’s External Research Program. This section is intended to provide an overview of the way in which CCNSW research investment contributes towards increases in knowledge, awareness and application of evidence into policy and practice.

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KPI 1: Measuring the level of funding and sustainability of Cancer Council NSW research

1.1 Maintain position as largest non-government funder of cancer research in NSW

CCNSW is the third largest funder of cancer research in NSW, behind the Federal government-funded NHMRC and the State government-funded Cancer Institute NSW. CCNSW holds an important position in the not-for-profit sector, as the largest non-government funder of cancer research in NSW (Figure 6).

Figure 6: Cancer Council NSW funding position 2011 and 2012 (KPI 1.1)

1.2 Maintain current level of funding allocated to cancer research

The research community values the level of support provided by CCNSW. Funds committed to cancer research are measured because it is important to preserve this funding level to sustain the momentum of cancer research activity in NSW. During the years 2011 and 2012, total CCNSW research expenditure remained around 30% of overall CCNSW expenditure (Figure 7).

$0

$10,000,000

$20,000,000

$30,000,000

$40,000,000

$50,000,000

$60,000,000

$70,000,000

$80,000,000

$90,000,000

$100,000,000

NHMRC Cancer InstituteNSW

Cancer CouncilNSW

National BreastCancer

Foundation

Cure CancerAustralia

Foundation

InternalResearchExpenditure

ExternalResearchExpenditure

15

Figure 7: CCNSW expenditure 2011 and 2012, with percentage of research expenditure (KPI 1.2)

Figure 8 shows CCNSW’s overall expenditure, and total expenditure on research (including the investment in both the Internal and External Research Programs), with the investment in the External Research Program accounting for between 14.8% (in 2007) and 19.3% (in 2011) of overall CCNSW expenditure.

Figure 8: CCNSW expenditure 2006-2012, with percentage of external research expenditure

65.9%

34.1%

2011

69.4%

30.6%

2012

Other missionrelated expenditure

Researchexpenditure

15.1%

14.8%

15.1% 15.3%

16.3%

19.3% 16.3%

$0

$10,000,000

$20,000,000

$30,000,000

$40,000,000

$50,000,000

$60,000,000

2006 2007 2008 2009 2010 2011 2012

External researchexpenditure

Internal researchexpenditure

Other mission relatedexpenditure

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1.3 Funding leveraged against CCNSW research investment

Ideally, research funding from one organisation acts as a catalyst to attract additional funding from other funding bodies generating further research and leading to further discoveries.

CCNSW’s external research investment has generated significant opportunities to leverage additional funding for cancer research. Against an initial CCNSW investment of $12.1 million in research projects that were completed in 2011 and 2012, a further $27.6 million was leveraged. This means that for every dollar CCNSW invested in those grants, the research teams have gone on to raise a further $2.28 to continue their research and ensure the sustainability of research momentum.

KPI 2: Measuring the linkages and the connection between research and practice

2.1 Evidence of procurement towards the application of research

The Common Scientific Outline (CSO; see Appendix 2) is an internationally recognised cancer research classification system. It is used widely within Australia and internationally and allows funding agencies to compare their research portfolios against those of other funding bodies and research institutions. This information can be used to determine the proportion of research investment directed towards the different classifications along the research continuum, to monitor patterns in research expenditure and, importantly, to guide future research investment strategies.

Of External Research Program funding committed during 2011 and 2012, the highest proportion was directed towards biological research (34.5%), followed by treatment (26.5%) and early detection, diagnosis and prognosis (16.8%), with research into prevention (8.6%), scientific model systems (6.1%), aetiology (5.9%) and cancer control, survivorship and outcomes (1.5%) enjoying relatively less support3 (Figure 9). Just over half of External Research Program funding (50.9%) committed during this period was distributed towards the application of research, namely Early Detection, Diagnosis, and Prognosis; Treatment; Cancer Control, Survivorship, and Outcomes; and Scientific Models Systems.

Figure 10 indicates that the distribution of CCNSW External Research Program funding across the CSO categories differs depending on the funding scheme. The STREP scheme focuses on research that will impact policy and practice, so it is not surprising to find that the distribution of funding covers Prevention; Early Detection, Diagnosis, and Prognosis; and Treatment. Innovator Grants are a STREP Stage 3 procurement strategy, based on priorities identified through the Stage 2 priority setting process. Given that the STREP Grants focus on translational research, it is logical that the majority of funding for Innovator grants is around treatment. Program and Project Grants fund investigator-initiated research, where funding distribution tends towards Biology for the majority, followed by Treatment.

3 Notably, significant CCNSW funding is directed to research into aetiology and cancer control, survivorship and outcomes through CCNSW’s Internal Research Program.

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Figure 9: Distribution of CCNSW External Research funding awarded in 2011 and 2012 across Common Scientific Outline categories, compared against all cancer research conducted in Australia and NSW in 2003-2005 (KPI 2.1)

Figure 10: Distribution of CCNSW External Research funding awarded in 2011 and 2012 across Common Scientific Outline classifications

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Cancer Australia’s report Cancer Research in Australia: 2003-2005 demonstrated that the distribution across NSW of cancer research funding from both government and non-government sources during the period 2003-2005 was clearly towards the basic science end of the spectrum, with the majority of research funded in biology (44%), followed by treatment (20%). This indicates that the distribution of CCNSW external research funding across CSO classifications does not differ greatly from all cancer research funding provided in NSW from 2003 to 2005 (Figure 9). This information provides CCNSW with an opportunity to review our funding priorities and consider directing a higher proportion of funding to under-resourced areas that attract low levels of funding from other sources.

2.2 Evidence of research involving consumers

CCNSW’s Consumer Participation in Research Program, developed and implemented in collaboration with Cancer Voices NSW, ensures that the research funded by CCNSW is of value to cancer consumers and the wider community. The Program’s first major achievements were its use of qualitative research methods to identify the values deemed by consumers and community members to be important in judging research, and subsequent development of an appraisal instrument to enable the inclusion of consumer and community values in CCNSW’s research funding decisions.4 Since that time, all researchers applying for CCNSW funding have been required to complete the consumer-specific appraisal tool in addition to their scientific applications. Under the other major components to the Consumer Participation in Research Program, CCNSW trains research consumers in the use of these appraisal methods, and each year convenes panels of these trained consumers to assess applications for research funding.

All applications for CCNSW research funding submitted during 2011 and 2012 were reviewed by consumers. This occurred through a Consumer Review Panel convened specifically to review all applications to a particular funding program, or via a consumer sitting on the broader Grant Review Committee (Table 6).

Table 6: Consumer participation in reviewing grant applications 2011 and 2012 (KPI 2.2)

Grant Type Year Consumer Review Panel

Consumer representative on Review Committee

Project 2011 √

2012 √

Program 2011 √ √

STREP 2011 √

Innovator 2011 √

Ideally, all CCNSW applications would be reviewed by a specially convened Consumer Review Panel, as this entails a more in-depth review of consumer criteria. Guidelines have since been implemented to ensure that all future STREP and Innovator grant applications 4 Saunders C, Girgis A, Butow P, Crossing S, Penman A. Beyond scientific rigour: Funding cancer research of public value. Health Policy 2007:84;234-242

http://canceraustralia.gov.au/sites/default/files/publications/national_audit_of_cancer_research_projects_and_research_programs1_504af02133667.pdf

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are reviewed by a Consumer Review Panel, with the Chair of that Panel also sitting on the broader Grant Review Committee.

The CCNSW Consumer Training program was not conducted in 2011. In 2012, CCNSW conducted the two-day training program, training 13 consumers who represented a range of geographical locations (metropolitan, regional, rural) and consumer roles (cancer patient, carer and survivors), including CCNSW’s first Aboriginal research consumer. Over the period 2011-2012, 138 funding applications were reviewed by consumers.

2.3 Evidence of supporting multidisciplinary research teams

The complexity of cancer means that a wide range of skills are needed to investigate research questions. No one individual has the knowledge, skills and expertise required to address these complex questions. Collaboration and the sharing of knowledge accelerates cancer research progress. CCNSW encourages collaboration among funded researchers.

The number of Chief Investigators of projects to which External Research Program funds were committed in 2011 and 2012 ranged from one to 12. Sixty-five percent of projects awarded funding during this period were led by two or more Chief Investigators. The number of Chief Investigators varies across funding programs (Figure 11). Project, Program and STREP funding schemes involve longer funding periods and higher amounts of funding, conditions which encourage larger research teams. In contrast, the Innovator Grant Scheme funds projects for a maximum of $100,000 for one year, and tends to attract proposals led by a single Chief Investigator.

Figure 11: Number of Chief Investigators per grant funded in 2011 and 2012, by funding scheme

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Across each of the main competitive funding programs, the average number of Chief Investigators on projects to which funds were committed during 2011 and 2012 was:

The number of Institutions involved in projects to which External Research Program funds were committed during 2011 and 2012 ranged from 1 to 7, with 47% of these funded projects involving researchers from a single Institution (Figure 12).

Figure 12: Number of institutions per grant funded 2011 and 2012, by funding scheme

The average number of institutions on grants awarded in 2011 and 2012 for each funding scheme was:

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Engaging an appropriate mix of disciplines to support research not only increases learning experiences, but builds capacity through developing research skills, and exchanging, expanding and enhancing knowledge. As part of a commitment to meeting KPI 2.3 (evidence of supporting multidisciplinary research teams), CCNSW aims to ensure that 100% of grants funded to a value of more than $300,000 per annum are awarded to multidisciplinary teams (defined as the representation of three or more disciplines on a research team). Of the grants funded for more than $300,000 per year to which External Research Program funds were committed during 2011 and 2012, just 33% were awarded to multidisciplinary research teams. In the absence of a current mechanism by which to ensure this objective is achieved, the Research Strategy Unit may consider incorporating this as an essential criterion during the research funding application and review processes for the larger (STREP and Program) Grants.

KPI 3: Measuring the quality, success and influence of research

3.1 Evidence of productivity and contribution to knowledge and evidence

Peer-reviewed publications are an accepted measure of research success and quality. Overall, for grants that ended in 2011 and 2012, projects supported under the Project Grant funding scheme produced the largest number of publications. However, STREP Grant research teams produced more publications per grant (Table 7). A number of factors contribute to these outcomes. CCNSW funds a higher number of Projects Grants, as they are smaller amounts of funding and over shorter periods of time, whereas Program and STREP Grants are longer term research projects supported by larger amounts of funding. Innovator Grants on the other hand are a short term project supported by smaller amounts of funding.

Table 7: Publications for grants that ended in 2011 and 2012 by CCNSW funding scheme (KPI 3.1)

Grant Type No. Publications

Mean no. publications per

grant

Mean no. publications per grant per year of

funding

Project Grants 140 4.5 1.5

Program Grants No Program Grants ended in 2011 and 2012

STREP Grants 80 40 8

Innovator Grants 9 1.5 1.5 3.2 Evidence of influence on knowledge and evidence

The impact factor of a journal reflects the average number of times articles published in that journal have been cited in the preceding two years. Notwithstanding the significant debate as to the utility of impact factors as a measure of research success (see for example, http://am.ascb.org/dora/), they have traditionally been used to compare different journals within certain fields, with higher impact factors deemed to reflect better quality journals, and indirectly, better quality research, than lower ones. For grants that were completed in 2011 and 2012, research teams funded under the CSO classifications of Biology, Aetiology, Prevention, Early Detection, Diagnosis, and Prognosis, and Treatment published their

http://am.ascb.org/dora/

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results in journals with higher impact factors than research teams that were funded under the CSOs Cancer Control, Survivorship, and Outcomes Research; and Scientific Model Systems. This is to be expected given that journals in these fields have lower overall citation rates (Table 8).

Table 8: Impact factors for publications arising from grants that completed in 2011 and 2012, by CSO

CSO Impact Factor Mean

Impact Factor Range

Biology 6.2 0 – 49.3

Aetiology 7.4 0 – 49.3

Prevention 6.9 0 – 49.3

Early Detection, Diagnosis, and Prognosis 5.9 0 – 49.3

Treatment 6.0 0 – 49.3

Cancer Control, Survivorship, and Outcomes Research 3.5 0 – 8.7

Scientific Model Systems 5.6 0 – 15 Across each of the main competitive funding schemes, the paper published during 2011 or 2012 in the highest impact factor journal is listed below.

Project: Cannons JL, Tangye SG, Schwartzberg PL. SLAM family and SAP adaptors in immunity. Annual Review of Immunology. 2011. 29: 665-705. IF = 49.27

Program: Shay, J.W., Reddel, R.R. Wright, W.E. Cancer and telomeres - an ALTernative to telomerase. Science. 2012. 336:1388-90. IF = 32.54

STREP: Phillips W, Lord RVL, Nancarrow D, Watson DI, Whiteman DC. Barrett’s oesophagus. J Gastroenterol Hepatol. 2011. 26:639-48. IF = 10.61

Innovator: Apte M, Pirola R, Wilson J. The Fibrosis of Chronic Pancreatitis : New Insights into the Role of Pancreatic Stellate Cells. Antioxidants and Redox Signalling. 2011. 15:2711-22. IF = 8.21

Another measure of research impact on scientific knowledge is article citation. Article citation is a measure of the number of published authors who reference a particular article in their own published work. The higher the number of times an article is cited, the more reach it has. Web of Science provides one measure of citations, but counts citations only in Web of Science publications. Google Scholar provides a search of further sources, therefore it is not surprising that the citation mean and range found on Google Scholar are larger than the citation mean and ranges from Web of Science. Table 9 shows that articles published by research teams funded under the Biology; Prevention; and Scientific Model Systems CSO’s have the same citation range of 0-13, while articles published by research teams funded under Aetiology; Early Detection, Diagnosis, and Prognosis; and Treatment CSO’s have similar citation range of 0-22. Articles published by research teams funded under the Cancer Control, Survivorship, and Outcomes Research CSO had a citation range of 0-9. Most academic journals have an expected citation rate, which indicates how often a paper is expected to be cited, based on its year of publication, journal and article type. Table 9 shows that for grants that were completed in 2011 and 2012, the percentage of publications that

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met expected citation at year one ranged from 50% for those funded under CSO classification Scientific Model Systems, to 65.7% for the CSO classification Early Detection, Diagnosis, and Prognosis.

Table 9: Citations for grants that completed in 2011 and 2012, by CSO (KPI 3.2)

Web of science Google

CSO Citations: Mean

Citations: Range

% of publications that met expected citation

at 1 year

Citations: Mean

Citations: Range

Biology 2.5 0 – 13 59.1% 5.3 0 – 44

Aetiology 3.3 0 – 22 58.2% 6.5 0 – 53

Prevention 2.9 0 – 13 61.1% 5.6 0 – 24

Early Detection, Diagnosis, and Prognosis

2.9 0 – 22 65.7% 5.8 0 – 53

Treatment 2.6 0 – 22 59.6% 5.2 0 – 53

Cancer Control, Survivorship, and Outcomes Research

1.9 0 – 9 52.6% 4.1 0 – 24

Scientific Model Systems

2.1 0 – 13 50.0% 4.6 0 – 24

Across each of the main competitive funding schemes, the paper published during 2011 or 2012 with the highest number of citations at year one is listed below.

Project: Erkan M, Adler G, Apte MV, Bachem MG, Buchholz M, Detlefsen S, Esposito I, Friess H, Gress TM, Habisch H-J, Hwang RF, Jaster R, Kleeff J, Kloppel G, Kordes C, Logsdon CD, Masamune A, Michalski CW, Junseo Oh J, Phillips PA, Pinzani M, Reiser-Erkan C, Tsukamoto H, Wilson J. StellaTUM: current consensus and discussion on pancreatic stellate cell research. Gut. 2012. 61(2): 173. Citations at year one = 13

Program: Lovejoy CA, Li W, Reisenweber S, Thongthip S, Bruno J, de Lange T, De S, Petrini JHJ, Sung PA, Jasin M, Rosenbluh J, Zwang Y, Weir BA, Hatton C, Ivanova E, Macconaill L, Hanna M, Hahn WC, Lue NF, Reddel RR, Jiao Y Kinzler K, Vogelstein B, Papadopoulos N, Meeker AK. Loss of ATRX, genome Instability, and an altered DNA damage response are hallmarks of the Alternative Lengthening of Telomeres pathway. PLoS Genetics. 2012. 8 (7): e1002772. Citations at year one = 14

STREP: Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, Colvin EK, Nagrial A, Chin VT, Chantrill LA, Samra JS, Gill AJ, Kench JG, Merrett ND, Das A, Musgrove EA, Sutherland RL and Biankin AV. The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Annals of Oncology. 2012 Jul;23(7):1713-22. Citations at year one = 13

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Innovator: Gong J, Jaiswal R, Mathys JM, Combes V, Grau GE, Bebawy M. Microparticles and their emerging role in cancer multidrug resistance. Cancer Treatment Reviews. 2012. 38(3):226-34. Citations at year one = 7

KPI 4: Measuring transparency

4.1 Evidence of research evaluation

CCNSW encourages transparency around reporting against our research indicators to demonstrate how our funding serves our mission of defeating cancer. Through transparent reporting, measures and assumptions about performance are exposed to public scrutiny. Feedback is welcomed.

KPI 1: Measuring the level of funding and sustainability of Cancer Council NSW research Indicator Goal Goal Status

1.1 Cancer Council NSW position as the largest non-government funder of cancer research in NSW retained

Cancer Council NSW ranks ≤ 5 in the largest cancer research funding charities in NSW

1.2 Current level of funding allocated to cancer research maintained

20% of annual budget dedicated to research (measured as a proportion of total expenditure, net of fundraising costs)

KPI 2: Measuring the linkages and connection between research and practice Indicator Goal Goal Status

2.1 Evidence of research procurement towards the application of research

50% of funding distributed across early detection, diagnosis, prognosis; treatment; cancer control, survivorship and outcomes; and research scientific model systems

2.2 Evidence of research involving consumers

% of funding decisions will involve input from trained consumer representative

2.3 Evidence of supporting multidisciplinary research teams

100% of teams funded at < 300k p.a. will be multidisciplinary

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KPI 3: Measuring the quality, success and influence of research Indicator Goal Goal Status

3.1 Evidence of productivity and contribution to knowledge and evidences

Project Grants: 0.67 publications per year of funding

Program Grants: 3 publications per year of funding

STREP Grants: 3 publications per year of funding

3.2 Evidence of influence on knowledge and evidence

50% of articles published will meet expected or baseline citation rates within their field

KPI 4: Measuring transparency Indicator Goal Goal Status

4.1 Evidence of research evaluation 100% of indicators reported

Key:

KPI goal not applicable

KPI goal reached

Significant progress made towards KPI goal

KPI goal not reached

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Research Outcomes:

Case Studies

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STREP Grant case study: Progression of Barrett’s Esophagus to Cancer Network (PROBE-NET)

Progression of Barrett’s Esophagus to Cancer Network (PROBE-NET) was a 2008 Strategic Research Partnership (STREP) Grant awarded in 2008 to Professor David Whiteman of the Queensland Institute of Medical Institute. This STREP brought together the existing activities of four leading independent Barrett’s oesophagus/ oesophageal cancer research groups in Australia into a coordinated national endeavour. Funding was used to establish a Barrett’s oesophagus tissue collection that is now among the largest of its type in the world, creating an invaluable resource for cancer researchers. CCNSW funded PROBE-NET for $1.25 million over the period 2008-2012.

The aim of PROBE-NET was to develop a reliable method to identify which patients with Barrett’s oesophagus will progress to cancer, to facilitate earlier detection of cancer and more effective treatment. PROBE-NET also aimed to develop national guidelines for the diagnosis and management of Barrett’s oesophagus.

Partnerships with Cancer Council NSW

This STREP benefited from two partnership opportunities with CCNSW. Former CCNSW CEO Dr Andrew Penman contributed his policy expertise to PROBE-NET and subsequent grant applications. There was also a research synergy with CCNSW’s internal Cancer Research Division, who during the PROBE-NET funding period led a study called InterSCOPE, which examined the role of HPV in squamous cell carcinomas of the oesophagus. A number of the same international experts were interested in both InterSCOPE and PROBE-NET. Professor David Whiteman became an InterSCOPE collaborator, which allowed for PROBE-NET to contribute their squamous cell carcinomas to InterSCOPE. In addition, scheduling meetings of the two studies around the same time allowed international experts to participate in both PROBE-NET and InterSCOPE.

During PROBE-NET Stage 2, PROBE-NET investigators, CCNSW staff and relevant Australian and international experts developed a set of research priorities considered likely to produce significant improvements in outcomes or breakthroughs important to people affected by Barrett’s oesophagus and oesophageal adenocarcinoma. The priorities were developed through structured interviews and subsequently refined through a nominal group process.

PROBE-NET Stage 2 Priorities

• Identify and evaluate treatments and response predictors for Barrett’s oesophagus and oesophageal adenocarcinoma

• Understand the biology of Barrett’s oesophagus and oesophageal adenocarcinoma • Develop better and more clinically relevant and practical identification and

stratification of patients in the population who are at risk of developing Barrett’s oesophagus and oesophageal adenocarcinoma

• Monitor patterns of care and outcomes for patients undergoing Barrett’s oesophagus surveillance and patients with oesophageal adenocarcinoma

• Develop Australian guidelines for patients with Barrett’s oesophagus and oesophageal adenocarcinoma

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• Address the need for greater capacity in Barrett’s oesophagus and oesophageal adenocarcinoma research

During PROBE-NET Stage 3, CCNSW’s aim was to develop procurement strategies to fund projects which addressed the priorities identified during Stage 2. This occurred through three mechanisms: calling for Innovator Grants which addressed these priorities; funding the development of a Clinical Trial Protocol; and setting a priority for Cancer Australia’s Priority-driven Collaborative Cancer Research Scheme which concerned pre-clinical trials of treatment targeting novel specific molecular pathways in cancer biology, with an emphasis on pre-cancers and cancers of the gastrointestinal tract. As a result of this procurement strategy, CCNSW continues to direct additional funds to research into oesophageal cancer beyond the PROBE-NET funding period.

Procurement Strategies

The following studies funded through different Cancer Council NSW funding programs arose directly from the PROBE-NET Stage 3 procurement strategy:

• A/Prof Wayne Phillips, Peter MacCallum Cancer Centre (Innovator Grant, $100,000, 2011) Using familial genetics to identify genes involved in the biology of Barrett’s Oesophagus

• Dr Sarah Thompson, Royal Adelaide Hospital (Innovator Grant, $94,255, 2011) Sentinel lymph node biopsy in oesophageal adenocarcinoma

• A/Prof Reg Lord, St Vincents Hospital (Clinical Trials Protocol, $50,000, 2011) Randomised trial of treatment for Barrett’s oesophagus

• Dr Lorraine O’Reilly, Walter and Eliza Hall Institute (Cancer Australia’s Priority-driven Collaborative Cancer Research Scheme, $590,000, 2013-2015) Understanding the role of NF-κB in the progression of gastric adenocarcinomas and assessment of new therapies

Knowledge and Discovery

The following outcomes were achieved during the five year PROBE-NET funding period:

• A national network of clinicians and researchers was established, including expansion to three new sites in 2012, namely Westmead Hospital (NSW), Greenslopes Hospital (QLD), and Nepean Hospital (NSW).

• A total of 7,147 tissue specimens were collected from 907 patients. A web-based database to keep track of these samples and to store the associated clinical data was designed, developed, tested and implemented.

• The PROBE-NET team developed common protocols, documentation, and forms to unify procedures at sites around the country.

• The extent of exchanged data and samples was high, leading to a number of publications utilising samples from more than one site.

• Thirty publications co-authored by one or more PROBE-NET investigators were published in journals with impact factors that range from 0 to 10.61 (average 3.172).

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• Four PhD students were enrolled on PROBE-NET scholarships, two of whom have had their degrees conferred.

• PROBE-NET hosted four national meetings, which included international researchers of high renown:

o 2009 Sydney: The ‘Frontiers in Barrett’s Oesophagus and Oesophageal Cancer’ Meeting;

o 2010 Melbourne: The ‘PROBE-NET Annual Scientific Meeting – partnered with the Australian Health and Medical Research Congress;

o 2011 Brisbane: PROBE-NET Annual Scientific Meeting – partnered with the international BEACON Meeting; and

o 2012 Adelaide: PROBE-NET Annual Scientific Meeting – partnered with the Australian Health and Medical Congress

Figure 13 is a citation tree of the highest cited paper published by the PROBE-NET research team. This citation tree illustrates the international reach of the paper, with authors from the USA, People’s Republic of China, Netherlands, Japan, Italy, Israel, Germany, England and Canada, citing this paper as informing their own publications.

Impact on Policy and Practice

An important focus of STREP funding is that the research has a direct impact on policy or practice. Following are four examples of how the PROBE-NET team have been involved in different committees to ensure that their research informs policy and practice:

PROBE-NET members are playing a leading role in the Barrett’s Neoplasia Guidelines Committee for Cancer Council Australia – Professor David Whiteman is the Chair of this Committee.

Professor David Whiteman is on the Steering Committee of the international Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON).

Professor David Whiteman has previously served on the US NCI Barrett’s Esophagus Translational Research Group (2008).

Professor Reginald Lord and Professor David Whiteman served on the Medical Services Advisory Committee Advisory Panel for Radiofrequency Ablation in Barrett’s Oesophagus (2010)

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Figure 13: Citation tree for Nancarrow DJ, Handoko HY, Smithers BM, Gotley DC, Drew PA, Watson DI, Clouston AD, Hayward NK &

Whiteman DC. Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High- Density Single-Nucleotide Polymorphism Arrays, Cancer Research (2008) 68:4163-4172.

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Return on Investment

An indicator of STREP success is the ability of the STREP team to leverage funding against the original CCNSW investment. PROBE-NET was highly successful in ensuring the sustainability of the research program beyond the end of the STREP funding period.

In 2008, CCNSW’s initial investment in PROBE-NET was $1.25 million. Since then Chief Investigator Professor Whiteman and his team have leveraged more than $7.6 million in additional funding for oesophageal cancer research in Australia and overseas; and total CCNSW investment in oesophageal cancer is now more than $1.77 million.

A significant part of this achievement is attributable to the success of PROBE-NET Professor Whiteman and his team in obtaining National Health and Medical Research Council funding to establish a multi-state, multi-disciplinary Centre of Research Excellence entitled PROBE-NET: The Progression of Barrett’s Esophagus to Cancer Network.

Centres for Research Excellence are an extremely prestigious form of funding for up to $2.5 million over five years to provide support for teams of researchers to pursue collaborative research and develop capacity in clinical, population health and health services research. This PROBE-NET achievement was enabled by the platform established by CCNSW’s original STREP funding.

The research team (listed below) is investigating possible causes of the disease, such as alcohol consumption, as well as the human genome, as they search for a treatment that will effectively target the cancer. The vision is to develop evidence-based strategies for reducing the burden of oesophageal neoplasia.

Chief Investigator • Professor David Whiteman – Queensland Institute of Medical Research

Co-Investigators

• Associate Professor Wayne Phillips – Peter MacCullum Cancer Centre • Professor Reginald Lord – St Vincent’s Hospital • Professor Nicholas Hayward – Queensland Institute of Medical Research • Professor David Watson – Flinders University • Associate Professor Andrew Barbour – University of Sydney • Professor Michael Bourke – University of Sydney • Associate Professor Guy Eslick – University of Sydney • Dr Andrew Penman – Former CEO, Cancer Council NSW

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Project Grant case study: Functional characterisation of the putative tumour suppressor gene MCC in colorectal cancer

MCC in colorectal cancer was a 2010 Project Grant awarded to Dr Maija Kohonen-Corish at the Garvan Institute of Medical Research. CCNSW funded Dr Kohonen-Corish for $360,000 over the period 2010-2012.

The MCC gene was discovered in 1991 due to its linkage with the APC gene, which is now recognised as a key tumour suppressor gene in colorectal cancer. However, MCC was overlooked for many years, because, unlike APC, it is only rarely mutated in colorectal cancer. Dr Kohonen-Corish’s team previously made the discovery that the MCC gene is defective in about 50% of colorectal cancers causing it to be expressed at low levels. This defect occurs in early premalignant polyps. The team developed a novel DNA based biomarker test that can identify the defective MCC gene in tumour specimens. The aim of this project was to determine how the MCC gene defect promotes cancer by studying cells grown in the laboratory and by examining surgical cancer specimens. This will determine which cellular functions are altered following loss of MCC in colorectal tumours. Ultimately this will determine if the MCC defect in cancer tissue is associated with improved or worse treatment outcomes in patients.

An understanding of the biological function of the MCC gene is needed in order to assess the value of MCC in predicting treatment responses. With this funding, the team have discovered three new biological functions for MCC which can now be tested further using preclinical models.


During the three year funding period of the MCC in colorectal cancer Project Grant the following outcomes were achieved:

• In year 1, the research team identified new phosphosites in the MCC protein and that one of these new phosphosites is responsible for regulating the DNA damage response function of MCC. This suggests that MCC silencing in the colorectal tumours would promote cancer because the ability of the cells to respond to DNA damage is impaired.

• In year 2, the research team demonstrated that poor short-term survival of patients with MCC-methylated colon tumours may be due to poorer responsiveness of MCC-methylated cancers to standard 5-FU based postoperative chemotherapy.

• In year 2, the research team also made the unexpected discovery of a second function of the MCC protein in the formation of lamellipodia. Ability to form lamellipodia may be important in ‘restitution’, which involves rapid resealing of the colon surface in response to injury. Thus, apart from a function in the DNA damage response, MCC may also be important in the barrier protection of the colon mucosa.

• In year 3, the research team worked on another new function of MCC. The team identified a potential mechanism by which the normally functioning MCC suppresses a major cancer promoting cellular pathway, beta-catenin. Hyperactivation of beta-catenin is found in the majority of bowel tumours and new evidence suggests that if MCC is defective in cancer cells, this defect contributes to hyperactivation of beta-

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catenin. This pathway is a promising target for drug therapies and finding a new mode of regulation may lead to novel approaches to treat cancer.

The research team’s next step is to study these functions further in their new MCC knockout mouse model.

In addition to these research findings, the research team also achieved the following outputs:

• Twelve publications were co-authored by one or more of the research team and published in journals with impact factors that range from 1.2 to 10.1 (average 4.2).

• Dr Kohonen-Corish was an invited speaker at three conferences in 2012. Additionally, over the three years of funding the research group presented fourteen oral and five poster presentations at both national and international conferences.

Return on Investment

In 2010, our initial investment in ‘MCC in colorectal cancer’ was $360,000. Since then, Dr Kohonen-Corish and her team have leveraged more than $2 million in additional funding for this specific area of colorectal cancer research in Australia. Total CCNSW investment in colorectal cancer is now more than $4 million.

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Program Grant case study: Building capacity in pharmacogenomics across NSW: PRIMe (Pharmacogenomic Research for Individualised Medicine)

Cancer pharmacogenomics research was first raised as a priority for CCNSW by Cancer Voices NSW consumer representatives at the November 2006 Cancer Research Committee. Through a Program Grant in Cancer Pharmacogenomics, CCNSW aimed to provide an avenue whereby researchers in NSW who have strong credentials in this area could align with therapeutics and clinical trials researchers to advance the practice of personalised medicine in cancer.

Building capacity in pharmacogenomics across NSW: PRIMe (Pharmacogenomic Research for Individualised Medicine) was a 2010 Program Grant awarded to Associate Professor Susan Henshall from the Garvan Institute of Medical Research, and funded for $1,498,668 over the period 2010-2014. Associate Professor Lisa Horvath replaced Associate Professor Susan Henshall as Chief Investigator in 2011.

Cancer patients need to know “How likely is it that this drug will work for me? How likely is it that this drug will harm me?” The PRIMe Program Grant brings together research and clinical programs from across NSW to create a unique network that is focused on understanding the biological basis of variation between patients in response to drugs that will result in the selection and delivery of the optimal therapeutic regimen for individual cancer patients.


PRIMe is mid-way through its funding period and so far has been able to:

• Harness existing capacity and build new capacity in anti-cancer pharmacogenomics in NSW through the establishment of a network of multicentre and multidisciplinary teams working in these areas to drive a coordinated and integrated effort in personalised medicine in cancer.

• Increase the number of participants enrolled in investigator driven pharmacogenomics studies by enabling multicentre recruitment, collection and biospecimens and patient data across the maximum number of sites across the network for use by established and developing research groups. This allows for the faster recruitment of patients and thereby reduces the timeframe that would otherwise be required before the results are published. As of June 2013, PRIMe has adopted eight studies from its group members and two interstate collaboration studies. The studies from its group members and their status are shown in Table 1. Studies that have now closed are currently being analysed and review for publication.

• Engage interstate and international teams to integrate and optimise the collective value of pharmacogenomics research in NSW and create opportunities for attracting as well as training individuals from both clinical and basic science backgrounds in pharmacogenomics research.

• Take a significant step towards establishing models for optimal clinical testing of pharmacogenomic assays and increasing the number of clinical trials of personalised medicine strategies for cancer.

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In addition to these achievements, the PRIMe team has presented three posters and three oral presentations at international conference, one of which as an invited speaker; and three posters and two oral presentations at national conference, one of which as an invited speaker.

Table 10: PRIMe studies and recruitment as at June 30

Studies

Number of patients recruited

Number of PRIMe sites

Recruitment Status

MIC-1 study (Prostate) 99 7 Active

TADE study (Breast) 128 2 Closed

TADE extension Study (Breast) 0 4 Newly Active

BNP study (Breast) 66 4 Closed

ADRI (Mesothelioma) 12 2 Active

DEEP-C Study (Ovarian) 60 2 Closed

IMPACT Study (Pancreas) 0 4 Newly active

PAST Study (Hepatosplenic) 19 2 Closed Return on Investment

In 2010, our initial investment in ‘PRIMe’ was $1,498,668. Since then Associate Professor Horvath and her team have leveraged more than $5.8 million in additional funding for this specific area of pharmacogenomics research in Australia. This means that for every dollar the CCNSW originally invested in this consumer priority, the research team has gone on to raise a further $3.87 to continue their research and ensure the sustainability of research momentum

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Appendices

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List of grants awarded 2011-2012

2011 Project Grants Professor Robert Baxter, University of Sydney. Targetting IGFBP-3 signalling pathways as a novel therapeutic approach in triple negative breast cancer.

Associate Professor Tracy Bryan, University of Sydney. G-quadruplex stabilisers as cancer therapeutics.

Doctor Megan Chircop, University of Sydney. Dynamin as a new drug target for the treatment of glioblastoma.

Associate Professor Peter Greer, University of Newcastle. Does the initial treatment plan predict doses delivered to normal tissues during prostate radiation therapy.

Doctor Beric Henderson, University of Sydney. Regulation of APC intracellular dynamics and function.

Doctor Viive Howell, University of Sydney. New opportunities for the study of ovarian cancer through characterisation of mouse models.

Doctor Tao Liu, University of New South Wales. The critical role of the histone demethylase JMJD1A in cancer.

Associate Professor Richard Lock, University of New South Wales. Predicting the in vivo sensitivity of paediatric acute lymphoblastic leukaemia to BH3-mimetic drugs.

Doctor Karen MacKenzie, University of New South Wales. The prognostic and therapeutic significance of dyskerin and telomerase enzyme activity in neuroblastoma.

Professor Finlay Macrae, Melbourne Health. The effects of butyrylated high amylose maize starch on polyposis in familial adenomatous polyposis volunteers.

Professor John Rasko, University of Sydney. The role of small non-coding RNAs (sncRNAs) in alternative splicing

Professor John Rasko, University of Sydney. Dissecting the multi-component machine that controls chromatin architecture.

Doctor Philip Vial, University of Sydney. A next generation detector for radiotherapy treatment verification with dual capability for simultaneous imaging and dosimetry.

Professor Robyn Ward, University of New South Wales. Laterally spreading tumours of the colorectum: an alternative pathway of colorectal cancer development in the Western world.

Associate Professor Xu Dong Zhang, University of Newcastle. Targeting Pro-Survival Mechanisms to Sensitize Human Melanoma to Immunotherapy.

2011 Priority-driven Collaborative Cancer Research Scheme Professor Robyn Ward, University of New South Wales. Role of dietary compounds on PGC-1 alpha methylation in colorectal cancer.

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2011 Program Grants Professor Philip Hogg, University of New South Wales. Metabolism inhibitors for the treatment of brain and pancreatic cancer.

Professor Murray Norris, Children’s Cancer Institute Australia for Medical Research. Toward cure of childhood ALL: improved diagnostics, therapeutics and prevention strategies.

Associate Professor Christopher Ormandy, Garvan Institute of Medical Research. Personalising breast cancer management by discovering the transcriptional basis of tumour phenotype.

Professor Roger Reddel, Children’s Medical Research Institute. Alternative lengthening of telomeres: from basic biology to drug discovery.

2011 Strategic Research Partnership Grants Professor Andrew Biankin, Garvan Institute of Medical Research. Genotype guided cancer therapy (Genomic Theranostics).

Laureate Professor Rob Sanson-Fisher, University of Newcastle. Newcastle Cancer Control Collaborative (New-3C).

2011 Innovator Grants Doctor Anthony Don, University of New South Wales. Developing sphingosine kinase 2 inhibitors to block glioblastoma cell proliferation.

Professor Georges Grau, University of Sydney. Deep sequencing of glioma derived microparticles.

Professor Lionel Hebbard, University of Sydney. Novel molecular targets fro treatment of hepatocellular cancer (HCC).

Professor Michael Murray, University of Sydney. Pharmacogenomic approaches to minimise sorafenib toxicity in patients with liver cancer.

Associate Professor Wayne Phillips, Peter MacCallum Cancer Centre. Using familial genetics to identify genes involved in the biology of Barrett’s Oesophagus.

Doctor Nicholas Shackel, The University of Sydney. Discovering novel non-invasive diagnostic and prognostic markers in hepatocellular carcinoma.

Doctor Sarah Thompson, University of Adelaide. Sentinel lymph node biopsy in oesophageal adenocarcinoma – improving staging accuracy & optimising treatment.

Doctor Kathy Willowson, University of Sydney. The role of imagable microspheres in radioembolisation treatment planning for HCC.

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2012 Project Grants Associate Professor Tracy Bryan, University of Sydney. Involvement of helicase DHX36 in human telomere maintenance.

Doctor Scott Cohen, University of Sydney. Structure and inhibition of the HumanTelomerase Enzyme complex.

Doctor Sue Firth, University of Sydney. IGFBP-3 enhances autophagy to promote breast cancer cell survival during stress.

Doctor Beric Henderson, University of Sydney. Novel regulation of beta-catenin intracellular transport and its role in cell polarity and migration.

Doctor Megan Hitchins, University of New South Wales. The mechanistic basis for prediction of response to alkylating chemotherapy in high grade glioma patients by molecular markers of MGMT activity.

Associate Professor Geraldine O’Neill, University of Sydney. A sting in the tail: Focal adhesion targeting and mechanotransduction.

Doctor Stuart Tangye, Garvan Institute of Medical Research. Mechanisms underlying impaired anti-EBV and anti-tumour immune responses in the absence of SAP.

2012 Priority-driven Collaborative Cancer Research Scheme Doctor Kerrie McDonald, University of New South Wales. Mechanisms underpinning how brain cancer cells respond to drugs.

Professor Anna Nowak, University of Sydney. Phase III trial of Concurrent & Adjuvant Temozolomide chemotherapy in non-1p/19q deleted anaplastic glioma.

Associate Professor Gianluca Severi, The Cancer Council Victoria. Risk and Prognostic Factors for Glioma in Australia.

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2

Common Scientific Outline

Biology 1.1 Normal functioning 1.2 Cancer initiation: Alterations in chromosomes 1.3 Cancer initiation: Oncogenes and tumour suppressor 1.4 Cancer progression and metastasis 1.5 Resources and infrastructure 1.6 Cancer related biology Aetiology 2.1 Exogenous factors in the origin and cause of cancer 2.2 Endogenous factors in the origin and cause of cancer 2.3 Interactions of genes and/or genetic polymorphisms with exogenous and/or endogenous factors 2.4 Resources and infrastructure related to aetiology Prevention 3.1 Interventions to prevent cancer: Personal behaviours that affect cancer risk 3.2 Nutritional science in cancer prevention 3.3 Chemoprevention 3.4 Vaccines 3.5 Complementary and alternative prevention approaches 3.6 Resources and infrastructure related to prevention Early Detection, Diagnosis, and Prognosis 4.1 Technology development and/or marker discovery 4.2 Technology and/or marker evaluation with respect to fundamental parameters of method 4.3 Technology and/or marker testing in a clinical setting 4.4 Resources and infrastructure related to detection, diagnosis, or prognosis Treatment 5.1 Localised therapies – Discovery and development 5.2 Localised therapies – Clinical applications 5.3 Systemic therapies – Discovery and development 5.4 Systemic therapies – Clinical applications 5.5 Combinations of localised and systemic therapies 5.6 Complementary and alternative treatment approaches 5.7 Resources and infrastructure related to treatment Cancer Control, Survivorship, and Outcomes Research 6.1 Patient care and survivorship issues 6.2 Surveillance 6.3 Behaviour 6.4 Cost analyses and health care delivery 6.5 Education and communication 6.6 End-of-life care 6.7 Ethics and confidentiality in cancer research 6.8 Complementary and alternative approaches for supportive care of patients and survivors 6.9 Resources and infrastructure related to cancer control, survivorship, and outcomes research Scientific Model Systems 7.1 Development and characterisation of model systems 7.2 Application of model systems 7.3 Resources and infrastructure related to scientific model systems

research investment evaluation 2011-2012

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