CCREP Annual Report 2012 by Simon Welch

Collaboration A key component of every day in research

ANNUAL REPORT 2012

PAGE Our Vision and Values

Chair’s Review of the Year

The Board of Trustees

General Manager’s Review of the Year

Clinical Director’s Review of the Year

Annual Research Highlights

Biostatistics Unit

Innovation and Awards

Middlemore Tissue Bank

Focus on Key Research Areas

Financial Statements

Independent Auditors’ Report

Directory 47 Staff List

CCREP ANNUAL REPORT - PAGE 1

CCREP’S

VISION & VALUES

CCRep is a registered charitable trust established in 2001 to facilitate and manage commercial clinical research and provide transparency of research and its related financial activities. Part of our role is to identify and contain the risks of research. CCRep is sited on the campus of one of New Zealand’s largest tertiary teaching hospitals, the 800-bed Middlemore Hospital in South Auckland, New Zealand. We also have access to a number of other large satellite facilities operated by the Counties Manukau District Health Board. The South Auckland region is home to unique patient populations accessible via well developed inpatient and community healthcare databases. We work closely with sponsors, researchers and investigators producing evidence to support the acceptance of new therapies.

Our Values

Our Strategy

Our Objectives

Our values flow from our Vision. CCRep is a leader in the field of clinical research and our people bring the capability, experience and quality required to achieve our goals.

CCRep’s strategic objective is to be the driving force for the development of an effective and efficient research culture at CMDHB.

• To undertake, conduct, promote, advance and fund research, audit, evidence-based practice and education

Goals: • To broaden the scope and client base within the existing strategy

• To assist the investigator in the set up and management of the research study

Commitment - showing care and respect for research participants

•

To build specific collaboration with, and between, CMDHB and the University of Auckland

• To develop and foster particular expertise in the health of Maaori and Pacific peoples

Research - delivering excellence in performance and clinical practice

•

To facilitate the link between clinical practice and research undertaken at CMDHB

• To disseminate information, results and findings

Experience - using expert knowledge for maximum benefit

•

To achieve scale and efficiency

Creativity - leading and innovating in health research

People - one team, working together with respect and integrity

• To promote educational programmes and material relating to research undertaken by CCRep • To form a relationship of mutual co-ordination and co-operation with the South Auckland Health Foundation • To develop relationships with similar bodies in New Zealand and internationally

CCREP ANNUAL REPORT - PAGE 2

CCREP ANNUAL REPORT - PAGE 3

CCREP BOARD OF TRUSTEES

CHAIR’S REPORT Fellow Trustees, CCRep’s tenth anniversary is a useful watershed, the appropriate time to consider the original aims of its establishment, how well they have been met and to take stock of the changes in its wider environment and their implications for our future. In a year which raised core questions about the model for clinical trial operations in New Zealand and its place in the public health system, CCRep continued to increase its activity by revenue, by breadth and intensity of research focus and by net result. At the same time the organisation began to adjust to its repositioning with Counties Manukau District Health Board. While there are transitional challenges in the clearer and narrower focus CMDHB has prescribed for its dealings with CCRep, the opportunities to engage in pan DHB work offer a more self-determining relationship model.

Murray Farnsworth Finance Manager

Lynda Mockett Business Manager CCREP ANNUAL REPORT - PAGE 4

Thank you for such consistent effort.

As these shifts and initiatives resolve in the year ahead CCRep will fundamentally review its strategy, structure and functional role within the regional and national industry.

Several trustees, mindful of the accomplishment of the organisation’s original purpose and wishing to enable fresh legs to carry it forward into the next phase, have stepped down during the year. They include the last two of the founding trustees – Drs Peter Gow and Harry Rea. They deserve particular gratitude for their long steady and thoughtful service and for their encouragement to map out a future in the new ecosystem. I also acknowledge the perspectives that Dr Wayne MacLean and Professor Rod Jackson brought to our table over many years. Continuing trustees have, pro tem, a larger burden until further appointments can be made based on clarity of future direction. Their gift of time and effort is appreciated.

Notwithstanding the uncertainties that such an air of change creates the organisation continues to evolve its operations to the scale and increasing complexity of its contracts while achieving efficiencies in time and human resources. The 2011 2012 net contribution brings total reserves to a healthy $1.9 million. It is worth noting that in the ten years it has taken to achieve this financial platform CCRep has also distributed $ 3.67m to the research funds at the disposal of CMDHB clinicians. It has taken the dedicated hard work of the staff and their constituency of investigators and researchers at CMDHB to conclude CCRep’s first decade with such a strong performance.

Mary Baldwin Research Nurse Manager

Ruth Withers Business Manager

Daphne Mason Tissue Bank Curator

Anne Blackburn

Dr Stuart Ryan General Manager

Yvonne Dunn Business Manager

Dr John Baker Clinical Director

CCREP’S

BOARD OF TRUSTEES

Ms Anne Blackburn (Chair)

Rod Jackson

Wayne McLean

Anne Blackburn has a background in banking, governance and strategic advice. She currently has appointments to the Boards of New Zealand Venture Investment Fund, UNITEC, Auckland Council Property Limited, Royal District Nursing Service New Zealand Limited, Forsyth Barr, Eastland Group, Fidelity Life and Warren and Mahoney. Anne is also a Trustee of the Ballet Foundation of New Zealand, the Chinese Language Foundation and the Sir Ernest Davies Diabetes Endowment Trust.

Rod Jackson is a professor of Epidemiology in the Section of Epidemiology & Biostatistics at the School of Population Health, University of Auckland. He is a member of the New Zealand College of Public Health Medicine. Rod is the academic leader of the PREDICT programme which uses a web-based clinical decision support system to get evidence about CVD risk and risk management, into and out of clinical practice simultaneously.

Ko Taupiri te maunga Ko Waikato te awa Ko Waikato tangata Waikato Taniwharau He Piko, he Taniwha he piko he Taniwha

Brad Healey (Deputy Chairperson) Brad Healey is the General Manager Medicine, Counties Manukau District Health Board. He has served on a number of Boards including health Alliance and Linkage Trust. Brad is a chartered accountant by profession and has worked in both Wellington and London with PricewaterhouseCoopers.

Alistair Burry Alistair Burry is a semi-retired financial governance consultant now spending time in various charitable activities, including CCRep, the Stellar Trust and the Eastern Bays Hospice Foundation. Previously, Alistair spent 16 years with the Fletcher Challenge Group in various senior Finance roles and later held the position of Chief Financial Officer for Metlifecare Ltd and senior Finance roles with Counties Manukau District Health Board.

Judy Kilpatrick Judy Kilpatrick leads the School of Nursing at the University of Auckland and in 1998 was awarded the Companion to the New Zealand Order of Merit for services to nursing education. Judy is an executive member of the Council of Deans of Nursing and Midwifery (Australia and New Zealand), and is a member of Universitas 21 group.

Don Mackie Born in the UK and educated in London, Don graduated from Manchester University Medical School and specialised in anaesthesia. Don has worked as an anaesthetist in hospitals large and small, including four years teaching at the University of Michigan. He also worked at Hutt Hospital as Clinical Head of the Emergency Department. He was Chief Medical Officer at Counties Manukau DHB from 2006 to 2011. In August 2011 he was appointed Chief Medical Officer at the Ministry of Health where he heads the Clinical Leadership, Protection and Regulation Business Unit and is taking a lead on health research.

Founding member of Raukura HauOra O Tainui, Mr McLean is also Chief Executive. He is an accountant by profession and has worked in the health arena for 28 years. Wayne has served on a number of Boards including the Health Funding Authority, Counties Manukau DHB, Waikato DHB and the National Health and Disability Advisory Committee. In addition to Raukura, Wayne chairs Hauora Waikato Maori Mental Health Service and also manages the North Waikato PHO.

Harry Rea Harry Rea is Professor of Integrated Care and Medicine, based at the South Auckland Clinical School. His background is as a respiratory physician and researcher. His current research interest is in the development of programmes of care for those with long term conditions (including COPD), and in particular, the integration of primary and secondary care.

CCREP ANNUAL REPORT - PAGE 5

GENERAL MANAGER’S

REVIEW OF 2011 THE YEAR July June 2012

Ten years on and CCRep continues to innovate. Clinical Conductor®, CCRep’s electronic clinical trial management system, has been fully implemented and has allowed us to eliminate a myriad of manual systems and processes. This is leading to improved efficiencies which will have a positive impact on our trial business in the coming year. The standardisation that has accompanied the installation of Clinical Conductor has laid the foundation for further development of a sophisticated quality programme (eQuIPCT) to be rolled out via CCRep’s intranet and based on the SharePoint® platform.

The CCRep model, based on international best practice, has grown and now delivers beyond the initial expectations. Since 2004 over 200 clinical trials have been completed; another 87 are currently in preparation or underway. CCRepmanaged trials take place within 18 hospital departments, ranging from Emergency Medicine and Surgery to the Kidz First Children’s Hospital and the National Burns Centre. In each case, CCRep interacts with CMDHB clinicians and staff to deliver research excellence. Accumulated funds from research surpluses and grants amounts to $4.89M while CCRep’s research practices adhere to the exacting requirements of the International Conference on Harmonisation Good Clinical Practice standards. CCRep is widely recognised in NZ as an industry-leading research management organisation and a CMDHB success story.

CCRep’s core purpose remains the conduct of clinical trials and support for the clinician-investigators that lead them. Clinical leadership is essential to the success of any clinical research project and at CCRep we work directly with over 76 investigators. With the support of CCRep many are undertaking their first research project; in 2011/12 eleven received funding via the CMDHB-CCRep Innovation Fund. An increasing proportion of CCRep’s activity is investigator-initiated NUMBER OF INVESTIGATORS and funded via grants andINawards. INVOLVED MANAGED CLINICAL In the period covered by thisTRIALS report YEAR ENDED 30 JUNE such research accounted for 28% of research projects compared with 26% 70 in the previous year. Our aim is to grow investigator-initiated research to 50% of 60 CCRep activity by resourcing a team to work with research partners and funders, 50 and specifically identify and develop high-quality 40 proposals for submission to funding agencies. 30

Commercial research managed by CCRep in the 2011/12 20 year, and undertaken by a collaborative team of clinician investigators,10research nurses and trial coordinators, generated $3.9M in revenue and returned over $430,000 to CMDHB 08 09 future 10 11 12 departments to support research YEAR

TRIALS BY TYPE

YEAR ENDED 30 JUNE

100 90 80 70 Number of Trials

Since its beginning 10 years ago, CCRep’s primary focus has been the support and facilitation of clinical research at Middlemore Hospital in partnership with South Auckland Health (now Counties Manukau District Health Board). In 2002 the fledgling organisation was charged with supporting academic clinicians, improving research quality, and growing the volume of research carried out in South Auckland. CCRep also supported the DHB by capturing and minimising identified financial, legal, regulatory and research risks as well as providing a vehicle for transparent and efficient management of research funds.

CCREP-MANAGED TRIALS TAKE PLACE WITHIN 18 HOSPITAL DEPARTMENTS, RANGING FROM EMERGENCY MEDICINE AND SURGERY TO THE KIDZ FIRST CHILDREN’S HOSPITAL AND THE NATIONAL BURNS CENTRE.

Innovation Fund Internally Funded Other Biotech Cognitive Device Pharma

50 40 30 20 10 08

10 11 YEAR

SPECIFIC FUNDS BALANCE

$4M 12 $3M

10 8

$2M 6 4

$1M

10 11 YEAR

CCREP STAFFING NUMBERS

CCREP ANNUAL REPORT - PAGE 6

YEAR ENDED 30 JUNE

INNOVATION FU NUMBER OF GR

YEAR ENDED 30 JUNE

10 YEAR

HIGHLIGHTS

HOSPITAL DEPARTMENTS INVOLVED

in Trial Revenue 2011/2012

Total accumulated funds from surpluses since inception

$430K

TRIALS

YEAR END

100 90

Added to Surplus Pool 2011/2012

80 70 Number of Trials

$3.9M $4.9M

60 50 40 30 20 10 08

NUMBER OF INVESTIGATORS INVOLVED IN MANAGED CLINICAL TRIALS

SPECIFIC

YEAR ENDED 30 JUNE

YEAR E

70 $4M 60 50

$3M

40 $2M

30 20

$1M 10

10 YEAR

STAFF CCREP ANNUAL REPORT - PAGE 7CCREP YEAR ENDE 40

GENERAL MANAGER’S

REVIEW OF THE YEAR

TRIALS BY TYPE

YEAR ENDED 30 JUNE

100

INVOLVED IN MANAGED

10 YEAR

10 11 YEAR

INNOVATION FUND NUMBER OF GRANTS

12 10 8 6

DISCONTINUED Sept 2011

CLINICAL TRIALS SPECIFIC FUNDS BALANCE It is very satisfying YEAR ENDED 30 to JUNEreport another YEAR ENDED 30 JUNE successful year for CCRep. Taking advantage of the skills within CCRep we 70 Dr Stuart Ryan $4M have been able to bring success to each 60 of activity as well as delivering a area sound financial result. It is my pleasure 50 to lead a team in which individuals,$3M at all levels of the organisation, are experts in 40 their field. As a result, trial participants $2M 30 receive gold standard care, investigators can rely on quality management processes 20 to be delivered consistently, and clients $1M can10be assured that service levels are comparable to international best practice. CCRep – creating the future of healthcare.

4 2

10 YEAR

NUMBER OF HOURS SPENT BY BIOSTATITICI ON CMDHB PROJECT (July 2011 – June 2012

CCREP STAFFING NUMBERS YEAR ENDED 30 JUNE

2200

1800 20

1400 1000

600 200 2008 Management

CCREP ANNUAL REPORT - PAGE 8

10 11 YEAR

2009

2010

Research and support

2011

2012

Clinical (nursing)

Other

CMDHB only

With the launch of Ko Awatea at CMDHB there has been a new energy surrounding research activity at Middlemore. From January to June 2012 preparation was made for the creation of a new Research Office within Ko Awatea. Resourced with five people, including the Biostatistics Unit managed by CCRep, this office will enhance the support for researchers at CMDHB. In addition, CCRep’s role at Middlemore from July 2012 has been focussed on commercial research activity,

Innovation Fund Internally Funded Other Biotech Cognitive Device Pharma

Joint projects

The Middlemore Tissue Bank has continued to develop in accordance with our Business Plan. We were delighted to have confirmed on-going funding support from the Freemasons Roskill Foundation, CMDHB, Leukaemia & Blood Cancer New Zealand, and CCRep. As a result, our growth strategy for the Tissue Bank is being executed. Two streams of work are on-going: firstly, to grow the biospecimen collection in number and variety, and work towards supplying researchers with samples; and secondly, to develop promotional material and avenues to publicise the presence and capability of the Middlemore Tissue Bank. As we gather momentum we look forward to developing new relationships to support our vision of seeking tomorrow’s cure.

the management and execution of90 80 projects funded by the Health Research Council of NZ, and the Middlemore70Tissue Bank. The clarity of purpose delivered 60 through this change will set the scene 50 for a challenging 2012/13 year for CCRep 40 as we review our strategic direction and 30 pursue a course which will deliver specific 20 of outcomes and benefits in each area responsibility. I am confident that CCRep 10 can meet the challenge and continue to demonstrate leadership within the NZ08 09 NUMBER INVESTIGATORS clinical trialsOFenvironment. Number of Trials

and education activities. Most participants in sponsored clinical trials are patients that would otherwise receive care via CMDHB. By receiving treatment via clinical trials, and from CCRep staff, these patients not only receive high quality care, they also have the potential to receive new and novel medication for a condition that may be rare or has failed to respond to usual care. CCRep collaborates with over 80 local and multi-national companies in testing new medications, devices and products which, in time, will become the future of healthcare in NZ.

CLINICAL DIRECTOR’S

REVIEW OF THE YEAR HIGHLIGHTS

62 7 1961

Pharmaceutical Sponsored Trials

Large Grant Funded Trials

Research participants on database

AS AT

JUNE 30 2012, CCREP WAS MANAGING 62 PHARMACEUTICALSPONSORED AND 7 LARGE GRANT-FUNDED CLINICAL TRIALS. THE PROVISIONAL SURPLUS TO SPECIFIC FUNDS FOR THE YEAR 2011-12 WAS 11.3% OF CLINICAL TRIAL REVENUE

CCREP ANNUAL REPORT - PAGE 9

CLINICAL DIRECTOR’S

REVIEW OF THE THE YEAR

CLINICAL TRIAL ACTIVITY

KO AWATEA

As at June 30, 2012, CCRep was managing 62 pharmaceutical-sponsored and 7 large grant-funded clinical trials. The provisional surplus to Specific Funds for the year 2011-12 was 11.3% of clinical trial revenue (i.e. NZ$437,758). This financial return on the clinical trial activity is on par with last year’s result and reflects a steady stream of new contracts as big Pharma recovers from the effects of the global financial crisis. With the transfer of the Research Office to Ko Awatea (see below), there is now capacity to permit limited growth of the business. A high level review has identified the potential for trial growth (mainly in Respiratory and Rheumatology areas) through the development of an appropriately equipped infusion room on-site within CCRep’s facility.

PUBLIC GOOD RESEARCH FUNDS

Professor Andrew Hill was appointed Director of Research for Ko Awatea in 2011. Andrew’s appointment has precipitated a number of changes for CCRep.

CCRep is the Host Organisation for submissions to the Health Research Council (HRC) originating from investigators based at Middlemore Hospital. There was only one CMDHB success in the last funding round.

The web-based Clinical Trial Management System (Clinical Conductor®) has been fully implemented. Data is stored in a remote New Zealand-based server and technical support is provided by the vendor (Bio-Optronics, US). Over the next year, CCRep will use this system to make improvements in operating efficiency, financial reporting, and productivity and further grow the in-house searchable database of potential clinical trial participants.

Research Office – On 1st July 2012, the Research Office was transferred from the Ground floor (CCRep) to the 2nd floor (Ko Awatea) premises. The former Research Officer (Alison Robertson) resigned and has been replaced by a fulltime Research Office Manager (Samantha Everitt) and a new fulltime Research Officer (Kathryn Askelund). Samantha and Kathryn are joined by the 3 former CCRep biostatisticians (Assoc. Prof Alain Vandal, Irene Zeng and Christin Coomarasamy). The services of the Research Office will be provided free of charge to CMDHB employees. Innovation fund – The CCRep Innovation Fund was discontinued from September 2011 and responsibility for its administration transferred to Ko Awatea.

Dr James Bartley. Vitamin D supplementation in Bronchiectasis – 12 months, $149,725

Preparing such applications is extremely demanding for colleagues who already hold fulltime clinical positions. CCRep has employed a Research Development Coordinator (Graham Knowles) to assist with grant preparation and submission and expect to have in place a part-time Biostatistician (in partnership with AUT University) by early 2013. CCRep has also accessed a professional medical writer who has assisted in drafting grant applications and journal manuscripts.

TRIALS BY TYPE

YEAR ENDED 30 JUNE

100 90

CCRep has employed a dedicated trial participant recruiter (Claire Reyneke) who is assisting research coordinators recruit for specific studies. Claire is using advertising campaigns, the call-centre function of Clinical Conductor and social media to add to our research participant database (current 1,961, target 10,000).

Number of Trials

70 60

Innovation Fund Internally Funded Other Biotech Cognitive Device Pharma

50 40 30 20 10 08

NUMBER OF INVESTIGATORS INVOLVED IN MANAGED CLINICAL TRIALS

YEAR ENDED 30 JUNE

70 $4M 60

10 11 YEAR

SPECIFIC FUNDS BALANCE

YEAR ENDED 30 JUNE

CCREP ANNUAL REPORT - PAGE 10

INNOVATION FUND NUMBER OF GRANTS

THE NZ HEALTH INNOVATION HUB The New Zealand Health Innovation Hub (iHub) was announced by the Ministers of Health and Economic Development on September 22, 2011. The iHub is a partnership between the four District Health Boards (DHBs); Counties Manukau, Auckland, Waitemata and Canterbury with backing from the Ministry of Economic Development, Auckland Tourism Events Economic Development and the Canterbury Development Corporation. The iHub is a national entity, with two regional delivery arms in Christchurch and Auckland. Dr Murray Horn was appointed as inaugural chairman and Sir Ray Avery as deputy chair. Dr Horn, who is also chair of the National Health Board, said “The best creative ideas often come from the frontline. We want to unleash the talent of New Zealand’s clinicians, and develop stronger relationships with industry to support innovation, and importantly, facilitate clinical trials of products, devices and systems developed in New Zealand. The Hub is a mobile, virtual organisation which will make the most of technology to deliver excellent customer service. Systems are

in place and expert advisors available to support innovators and fast-track ideas with the potential to improve health outcomes and be sold worldwide”. It is still not yet clear how this new development will affect CCRep. There have been some discussions about an ‘effective clinical trial network’ encompassing the 4 DHBs which may streamline internal approval processes and speed up the initiation of new sponsored clinical trials. However, it remains to be seen how this will eventuate.

CHANGES TO THE HEALTH & DISABILITY ETHICS COMMITTEE STRUCTURE IN NEW ZEALAND In February 2010, the NZ Parliament commissioned a select committee inquiry into ways of improving New Zealand’s clinical trials environment. The select committee tabled a report in June 2011 with 54 recommendations. The Minister of Health responded in September 2011 agreeing to take action on many of the recommendations. The changes include a modified ethics committee structure

(4 committees instead of 7 committees), simplified application forms, an electronic submission process, more rapid response, and more extensive use of the expedited review process for low risk studies. The standard operating procedures for ethics committees were overhauled and the changes were implemented on July 1, 2012. For CMDHB, this means taking responsibility for locality approval and scientific peer review of research proposals. For CCRep, this means a quicker turnaround in obtaining regulatory approval for sponsored clinical trials. Because competitive recruitment applies to most of our studies, the faster start-up of clinical trials will improve our business competitiveness.

Dr John Baker

CCREP ANNUAL REPORT - PAGE 11

RESEARCH HIGHLIGHTS

CCRep 10th Anniversary

Clinical Conductor®

In February 2002 CCRep and South Auckland Health (now CMDHB) signed a contract to give life to the vision of establishing a dedicated research institute at Middlemore Hospital. Ten years on CCRep is a centre thriving on collaboration.

CCRep is the first clinical trial site in NZ to use a comprehensive electronic Clinical Trial Management System (CTMS). Implementation has been staged due to the volume of trial activity to be transfered into the system and training requirements for staff. Representitives of the US vendor of Clinicial Conductor®, Bio-Optronics, travelled to NZ in September 2011 to provide on-site training and help with setting up the system. Entry of clinical trial information and transfer of our participant database was complete by November 2011; additional staff training was conducted by Richard Ames (CCRep’s dedicated CTMS Administrator). This phase generated considerable interest and enthusiasm among CCRep staff allowing progress to stage 2 in March 2012.

The original concept of creating a research institute at Middlemore Hospital was investigated in 1999. Local and international models were examined and as a result it was decided that a charitable research trust was the best vehicle to achieve the desired goals. The new institute was founded in 2001 and had a vision “To lead research in health and healthcare services; and to champion improvements in clinical care and delivery, based on information, evidence and new technologies.” Today, in 2012, CCRep is involved with the conduct of over 100 clinical trials each year and in the last few years has established a cancer tissue bank whose aim is to support translational research and development of new treatments for people with cancer. Relationships with over 90 different research and development organisations mean that CCRep is well placed to remain strong and contribute to creating the future of healthcare in New Zealand. CCRep celebrated this milestone with two open days to educate the public on our presence at Middlemore and our research processes. In addition, two CCRep Research Nurses, Renee Coxon and Julia Leary, celebrated 10 years of service to the organisation at a special staff lunch held in March 2012.

CCREP ANNUAL REPORT - PAGE 12

The second stage focused on consistency of utilisation so that Clinical Conductor® would become the single source of all CCRep trial information. Hands-on workshops for each therapeutic area occurred in March to ensure all staff had the support they needed and that all issues were resolved. By June 2012 the system was ‘live’ allowing the manual systems to be discontinued. Clinical Conductor® now plays a key role in the standardisation of CCRep’s trial processes and aligns well with our Quality Improvement Programme activity. Middlemore Tissue Bank CCRep’s Middlemore Tissue Bank initiative has continued to thrive. An additional 3 years of operational funding from our Founding Sponsor, Freemasons Roskill Foundation, has been confirmed. Additional funding support has been obtained from CMDHB (2 years) and CCRep (3 years). New funding from Leukaemia & Blood Cancer New Zealand to employ a haematology collection technician (2 years) will ensure that the tissue

collection continues to grow. Substantial effort has been made this year to complete the infrastructure, governance processes and sample collection procedures to enable efficient operation and, while largely invisible, this will set the stage for the Middlemore Tissue Bank to begin supporting cancer researchers and prospective collection projects over the next 12 months. HRC Funding CCRep will be the host institution for a successful feasibility grant from the Health Research Council (HRC) for Dr Jim Bartley’s project entitled “Vitamin D supplementation in bronchiectasis”. This grant was for $149,725 and the project will launch in October 2012. SHIVERS: Southern Hemisphere Influenza Vaccine Effectiveness Research & Surveillance CCRep was pleased to be chosen to partner with NZ’s Institute of Environmental Science & Research (ESR) in undertaking the SHIVERS project, funded by the US Centers for Disease Control. The SHIVERS project will look at how the influenza virus and other respiratory pathogens spread through populations. The results will be used to inform public health and vaccination strategies around the world in an effort to protect the most vulnerable patients and to better plan for, and protect against, flu epidemics and pandemics, such as Swine Flu. Drs Conroy Wong and Adrian Trenholme are leading the CMDHB/CCRep research teams in the adult and paediatric settings, respectively.

EMBRACE trial In May the results of the Health Research Council (HRC)-funded EMBRACE trial, led by Dr Conroy Wong and managed by CCRep, were published in The Lancet. In a field in which there is little empirical information to guide treatment, this trial showed that long-term, low-dose azithromycin was able to substantially reduce the rate of pulmonary exacerbations in adult patients with non-cystic fibrosis bronchiectasis. Key findings of the EMBRACE Trial:

a significant reduction in event-based exacerbations in the treatment group compared with the placebo group (42 vs 103, respectively);

time to first exacerbation within six months was significantly increased in the treatment group (hazard ratio = 0.337).

Dr Wong was awarded a second HRC grant in May 2011 to investigate whether

tiotropium is an effective treatment for bronchiectasis. This funding has allowed the multicentre network established for EMBRACE to be sustained. Led by the CCRep team at Middlemore Hospital, the ROBUST trial is also being conducted at Auckland City Hospital and Waikato Hospital.

The Lancet, Volume 380, Issue 9842, Pages 660 - 667, 18 August 2012

NZACRes CCRep was a bronze sponsor of the 2011 New Zealand Association of Clinical Research (NZACRes) conference held from 8-9 August at Sky City in Auckland. The CCRep Exhibition Booth showcased CCRep’s clinical trial capabilities and the newly-formed Middlemore Tissue Bank. This conference is a highlight on the NZ clinical research calendar and provided CCRep with a great opportunity to present our organisation at a significant national event.

IRL CCRep has continued to build on its relationship with Industrial Research Limited (IRL), a Crown Research Institute. Our initial contribution in providing clinical consulting and guidance on early stage initiatives has developed into early phase testing of new technologies being developed by IRL. CCRep has been included as one of seven partners in a new IRL funding bid to the Ministry of Science and Innovation in the Bold Ambitions in Medical Devices category. The outcome of the bid is due for release in September 2012. CCRep is also working with IRL on a joint bid for Health Research Council (HRC) funding for a project entitled “Does intensive insulin therapy promote healing in diabetic foot ulcers?” which will be submitted to HRC in October 2012.

CCRep at the 2011 NZACRes conference

CCREP ANNUAL REPORT - PAGE 13

BIOSTATISTICS UNIT

In the period covered by the present report, CCRep biostatisticians provided 2380 hours of support to research and audit activities across more than 36 different departments and units in CMDHB. Activities included project conceptualisation, study design, protocol development, study monitoring, data management, data analysis, result interpretation, dissemination, training, supervision and scientific evaluation. Most projects were observational studies, clinical trials and clinical audits along with some diagnostic studies and methodological research. Some projects were compulsory or were part of voluntary training activities for registrars and new staff. In the past financial year, the biostatisticians supported approximately 140 projects based at CMDHB through design, analysis, dissemination, or a combination thereof. The direct impact of these supporting activities is to enable the investigators to disseminate their research or audit results through presentations at local and international conferences and publications in peer-reviewed medical journals. The long-term impact of this support is translation of results into clinical practice and, eventually, improvement in patient outcomes.

2380

Hours of support

CCREP ANNUAL REPORT - PAGE 14

ONE HUNDRED AND THREE CMDHB STAFF USED CCREPâ&#x20AC;&#x2122;S BIOSTATISTICAL SERVICES. THEY CONSISTED OF 24 CONSULTANTS, 40 REGISTRARS OR RESEARCH FELLOWS, 12 NURSE SPECIALISTS AND 27 OTHER STAFF. CCRep biostatisticians also carried out contracted research activities involving 7 different commercial and non-commercial institutions: Pacific Edge Biotechnology, Living Cell Technology, Labtests, the Auckland Spinal Rehabilitation Unit, the Interdisciplinary Trauma Research Centre, the Centre for Physical Activity and Nutrition Research, and the Health and Rehabilitation Research Institute, the latter three being institutes at AUT University. All had involvement with investigators from CMDHB. Four international projects were supported over the last 12 months. This work was undertaken by the CCRep/ AUT academic biostatistician who also supervised two international interns hosted by CCRep for 2 months in 2012 (one in respiratory medicine, the other seconded to the AUT Gambling and Addictions Research Centre). The academic biostatistician was also involved in project peer-review as a member of the Health Research Councilâ&#x20AC;&#x2122;s (HRC) Career Development Award Committee for the year 2012.

One successful feasibility application to the Health Research Council was supported by the biostatisticians. The biostatisticians also provided support in the form of data monitoring and redesign of two funded research projects. A key activity undertaken by the biostatisticians is the Middlemore Statistics Clinic. The Statistics Clinic is held every two or three weeks, depending on the time of year, and usually accommodates four or five 45-minute appointments. About 15% of first appointments relate to statistical education or literacy; 25% relate to analysis of collected data, and the rest concern the design of studies. The Statistics Clinic provides an excellent forum for investigators to discuss their project, whatever its stage of development, with biostatisticians, who provide expert advice regarding design. The philosophy and dedication of the biostatisticians extends to attending meetings requested by investigators outside regular hours. Data analysis forms the final stage of a research project and usually consumes the bulk of biostatistical resources allocated to a project. Over the past year, the main data analytical efforts were expended on behalf of the Compliance and Amputation Study (approximately 170 person-hours; Baker et al.), and the Asthma Utility of Inflammometry in Diagnosis Study Study (about 140 person-hours; Garrett J. et al.). In addition, data from 15 CCRep Innovation Fund projects were analysed and reported.

A.Prof Alain Vandal (Academic Biostatistician) Irene Zeng (Biostatistician) Christin Coomarasamy (Data Analyst)

YEAR

NUMBER OF HOURS SPENT BY BIOSTATITICIANS ON CMDHB PROJECTS (July 2011 â&#x20AC;&#x201C; June 2012)

CCREP STAFFING NUMBERS YEAR ENDED 30 JUNE

2200

1800 20

1400 1000

PROJECTS (140) SUPPORTED BY CCREP BIOSTATISTICIANS BY DEPARTMENT (JULY 2011-JUNE 2012)

600 200

Gastroenterology

2008

Management

2009

2010

Research and support

2011

2012

Clinical (nursing)

Other

Respiratory

CMDHB only

Joint projects

PROJECT NUMBERS

Gynaecology and Obstetrics Orthopaedics External Institutions General Surgery Anaesthesia Haematology Endocrinology Pathology Otolaryngology National Burns Centre Home Health Care Plastic Surgery Paediatric Other CMDHB CCRep AT&R Stroke Speech Language Therapy Rheumatology Ophthalmology Nutrition Services Mental Health Infectious Diseases Gerontology Dermatology Cardiology Blood Bank Renal Physiotherapy Pharmacy Oral Health Intensive Care Unit Health Intelligence Unit

IN BRIEF

103 40 24 22

CMDHB staff involved

Registrars

Consultants

Nurses

Emergency Medicine

CCREP ANNUAL REPORT - PAGE 15

CCREP

INNOVATION FUND

The CCRep Innovation Fund was established as a joint fund between CMDHB and CCRep in 2008 with the aim of encouraging researchers from all healthcare professions to undertake small research projects, pilot studies or initiatives that are original and will contribute to achieving positive outcomes for the community of South Auckland. Awards of up to $10,000 were given to projects that addressed important local issues, specifically those identified in the CMDHB District Annual Plan and District Strategic Plan. Applicants were to be CMDHB staff only and projects had to be completed within 12 months. In addition to the grant funds, recipients also received free access to CCRep education workshops, were linked with an experienced mentor, and had priority access to CCRep statisticians. In 2012 the CCRep Innovation Fund was transferred to the new Ko Awatea Research Office (KARO) within CMDHB. As a result the current fund will cease to exist but ongoing projects will be supported by KARO until they are completed. Over the last 4 years from 2008-2011 the total grant funding awarded was $249,434 across 31 projects. Diabetes/ endocrinology received the most grants (5) followed by Respiratory Medicine (4) and Dietetics (3). As at June 2012, 17 projects had been completed with final reports received and many of these were either published in peer-reviewed journals or were being prepared for submission.

CCREP ANNUAL REPORT - PAGE 16

HIGHLIGHTS Effectiveness of splinting post Dupuytren’s Contracture release Shirley Collocott, Julie Collis This single-centre randomised trial looked at the effects of night splinting following surgical release of Dupuytren’s contracture. The results showed that night extension splinting in combination with standard therapy has no greater effect on maintaining finger extension than hand therapy alone in the three months following surgery. These findings indicate that the practice of night splinting may no longer be justified. These results were presented at CMDHB ScienceFest (June 2012) and the Hand Surgery Society Conference (Australia - August 2012). The results will also be presented at the New Zealand Association of Hand Therapists conference in November 2012.

Intraosseous antibiotic prior to total knee joint replacement Simon Young, Brendan Coleman, Joshua Freeman Reported rates of deep infection following Total Knee Joint Replacement (TKJR) persist between 1-2.5%. Prophylactic antibiotics are effective in reducing this devastating complication. This study looked to assess the efficacy of an alternative dosing route. This technique of intraosseous regional administration achieved tissue levels of prophylactic antibiotic an order of magnitude higher than conventional systemic administration. These results have been presented at the Royal Australasian College of Surgeons Annual Scientific Meeting (Queenstown – 2011), Closed Meeting of the Knee Society (Ontario – 2011), NZ/Australian Combined Orthopaedic Meeting (Rotorua – 2011). The paper was also presented at the Regsitrar Paper Day at Auckland City Hospital where it won best paper. Most recently the results were published in the journal Clinical Orthopaedics and Related Research.

IN BRIEF

$249K 31 17 Of funding provided

Projects Benefitting Cutaneous lupus and vitamin D levels at CMDHB

TRIALS BY TYPE

YEAR ENDED 30 JUNE

Paul Jarrett, Robert Scragg, Alistair Stewart

100 90

This project formed the second study of Paul Jarret’s MD thesis entitled “Skin disease and Vitamin D”.

Studies Completed

The first study looked at prevalence of cutaneous lupus in the CMDHB catchment area. This study followed on and looked at clinical examination and venesection of patients identified as having lupus in the initial prevalence study. A total of 80 patients were assessed for lupus status and vitamin D levels. This evaluation was undertaken with the assistance of the Innovation Grant. These results are NUMBER OF INVESTIGATORS currently being analysed. INVOLVED IN MANAGED

Number of Trials

70 60

Innovation Fund Internally Funded Other Biotech Cognitive Device Pharma

50 40 30 20 10 08

CLINICAL TRIALS

This will be followed on with anYEAR ENDED 30 JUNE intervention study using vitamin D 70 in psoriasis. It is anticipated that the completed thesis will be submitted in 60 2016.

10 11 YEAR

SPECIFIC FUNDS BALANCE

INNOVATION FUND NUMBER OF GRANTS

YEAR ENDED 30 JUNE

$4M 12

$3M

8 $2M

30 20

DISCONTINUED Sept 2011

6 4

$1M 10

10 YEAR

10 11 YEAR

CCREP STAFFING NUMBERS YEAR ENDED 30 JUNE

10 YEAR

NUMBER OF HOURS SPENT BY BIOSTATITICIANS ON CMDHB PROJECTS (July 2011 – June 2012)

CCREP ANNUAL REPORT - PAGE 17 30

2200

CCREP

INNOVATION FUND SUCCESSFUL GRANTS

2008 Weigh in weigh out Dietitics

$8,900

Franica Yovich, Andisha Maido Sarcomas of the vulva and vagina Histopathology $5,130 Susan Bigby, Michael Dray Real-time multiplexed tandem PCR Microbiology $10,000 Susan Taylor, Arlo Upton, Pat Mead, Roger Stamp Untreated psychosis Psychiatry

$9,180

2010

2011

Stress and apical ballooning syndrome Cardiology

Care of diabetic adolescent and young adult Diabetes

$4,555

June Poole, Jodie Main, Caitrin Roberts, Lorraine Morley, Katherin McLean, Irene Zeng Live well pilot programme Dietetics

$9,593

Hannah Cullinane, Jonathan Kwan Barriers to care in patients with type II diabetes and vision threatening retinopathy Diabetes $7,094

Ian Soosay, Aaron O’Connell, Rob Kydd

Naomi van der Merwe, Roshni Prakash

Procalcitonin bronchiectasis Respiratory $10,000

Effectiveness of splinting post Dupuytren’s contracture release Occupational Therapy $5,880

Conroy Wong, Susan Taylor, Lata Jayaram, David Holland, Sarah Mooney

Shirley Collocott, Julie Collis Is the electronic discharge summary effective as a communication tool? Diabetes $9,887

2009 Control of dyspnoea Respiratory

$10,000

Fiona Horwood, Diana Hart, Anurajith Seneviratna, Gray Maingay, Nicol Corna, Irene Zeng Troponin I study General Medicine

$4,334

Teddy Wu, Edward Wong, Mr Ajay Kumar, Danial Garafalo Hypo-pack for diabetics Diabetes

$4,200

Claire O’Brien, Elaine Chong, Elham Hajje, Doreen Liow Intradermal vs subcutaneous anaesthesia Respiratory $6,165 Charlene Swanevelder, Hong Anh Nguyen, Nicola Corna, Irene Zeng, Conroy Wong

Theresa Busler, Judith Dee Intraosseous antibiotic prior to TKJR Orthopaedics $10,000 Simon Young, Brendan Coleman, Joshua Freeman Cutaneous lupus and vitamin D levels in CMDHB Dermatology $6,152

$7,524

Angela Knox, Suzette Norris, Samar Issa Nocturnal hypoxaemia and gout Respiratory $8,466 Christine Little, Shyama Abraham, Fiona Horwood Identifying barriers to antenatal care among women who book late in pregnancy Obstetrics & Gynaecology $9,454 Sarah Corbett, Kara Okesene-Gafa Validation of e-nutrition screening in a primary health care setting Dietetics $9,995 Sandra Van Lill, Shankar Sankaran

CCREP ANNUAL REPORT - PAGE 18

Carl Eagleton, Gill Aspen, Claire O’Brien, Diane Bermingham, Brandan Orr-Walker Effect of group music therapy Mental health $7,852 Ajay Castellino, Sarah Hoskyns, Mark Fisher, Irene Zeng, Allyson Waite Colestipol as a phosphate binder Renal $10,000 Chris Hood, Mark Marshall, Jamie Kendrick-Jones Novel ankle diastasis intraoperative stress test Orthopaedics $1,955 Francis Ting, Lyndon Bradley, Brendan Coleman Safety, pharmacokinetics and pharmacodynamics of metformin treatment in patients with metformin-naïve type 2 diabetes and advanced chronic kidney disease Diabetes $10,000 Ajith Dissanayake, Chris Hood, Mark Marshall, Alain Vandal Use of sailing simulator technology to enhance wellbeing and activity levels in people with spinal cord injury Physiotherapy $10,000 Lavinia Buchanan, Paula Cunningham

Paul Jarrett, Robert Scragg, Alistair Stewart Survivorship study for haematology patients Haematology

$9,090

Preventable hospital-associated thromboembolism study Haematology $9,264 Martyn James, Gordon Royle The optimal duration of pulmonary rehab to enhance health outcomes at CMDHB: a pilot study Physiotherapy $7,935 Sarah Candy, Diana Horner, Brigitte Eastwood, Sarah Mooney, Dr Fiona Horwood Perioperative troponin I rises, composite cardiac outcome and 30 day mortality in patients undergoing surgery for fractured NOF Anaesthesia $9,715 Julian Dimech, Matthew Taylor, Joanna Sinclair, Ruvin Gabriel, Sunita Paul, Brendan Coleman What does suctioning do to premature infants needing help with their breathing and does how often they are suctioned make a difference? Neonatal Unit $7,207 Su Greensill The lived experience of the competency review process Nursing Dianne Barnhill, Jens Hansen, Willem Fourie, Amanda Browne

$9,907

TISSUE BANK

REVIEW OF THE YEAR

As we gather momentum we look forward to developing new relationships to support our vision of seeking tomorrowâ&#x20AC;&#x2122;s cure.

CCREP ANNUAL REPORT - PAGE 19

MIDDLEMORE TISSUE BANK

GOVERNANCE COMMITTEE – CHAIR’S REPORT The Governance Committee has played its part in an important phase of the establishment of the Tissue Bank. Care has been taken to ensure there has been no departure from the high standards set for its early collections and this has been supported by the Scientific and Operations Committees. Experience has been built up in the consenting process of the collection. The Committee realises the importance of winning the willing consent of tissue donors for our work. Documentation has been prepared for making available the specimens to cancer researchers from whom there is increasing regional interest. Co-operation with other cancer research bodies as well as academic researchers will be strengthened in the coming year as we enable researchers to readily identify what is held as well as what can be collected for prospective research. Through international contact we have been able to follow best practice and learn from the experience of others in the field. In this we particularly value the contribution of Dr Anne Thompson, Executive Officer of the Victorian Cancer Biobank in Melbourne who is an active member of this Committee. The Committee acknowledges the great support of the Founding Sponsor, the Freemasons Roskill Foundation, as well as the specific support of Leukaemia and Blood Cancer New Zealand. It will be essential to widen the base of financial support to sustain and grow the Bank beyond its establishment phase. For this it will be necessary to make the tissue bank at Middlemore better known.

CCREP ANNUAL REPORT - PAGE 20

In the meantime the rate of collection of tissue will need to accelerate to reach a critical mass. Then we will be able to demonstrate the significant contributions to cancer research which tissue banking can make. The committee has met regularly during the year and has been impressed with the energy and dedication of Dr Stuart Ryan, Dr Samar Issa and Daphne Mason who have brought the vision into being carefully step by step. Their work has created a foundation for research to seek tomorrow’s cures. I also thank the members of the Committee who have given unstintingly of their time and wisdom to our governance role. Sir Bruce Slane Chair Governance Committee

Governance Committee Members Gillian Cossey General Manager Surgery, CMDHB Pru Etcheverry Executive Director of Leukaemia & Blood Cancer New Zealand. Adina Halpern Barrister and Solicitor David Mace Chair, Freemasons Roskill Foundation Sir Bruce Slane Chair, Middlemore Tissue Bank Dr Barry Smith (Te Rarawa, Ngāti Kahu) Chairman, Lakes DHB Research and Ethics Committee Anne Thompson Executive Officer, Victorian Cancer Biobank

MIDDLEMORE TISSUE BANK

CLINICAL DIRECTORâ&#x20AC;&#x2122;S REPORT

3436 2379 225%

Total Biospecimens

Cancer is the leading cause of death in NZ (29%) and a major cause of hospitalisation. Most New Zealanders will have some experience of cancer, either personally or through a relative or friend, with 1 in 3 New Zealanders affected by cancer in some way. Every day around 51 people are diagnosed with cancer in New Zealand and there are 22 cancer deaths. There are 4,990 new diagnoses and 2,029 deaths each year in Auckland alone. Unfortunately, more people are developing cancer, mainly because of population growth and ageing. The Middlemore Tissue Bank was launched in June 2009 to meet our local cancer researchersâ&#x20AC;&#x2122; needs and provide them with a diverse collection of tumour biospecimens. The operational committee oversees the collection of tissue samples at Middlemore Hospital and has been instrumental in facilitating expansion of the collection. Our partnership with Leukaemia & Blood Cancer New Zealand was strengthened in 2012 through the awarding of a grant that allowed us to employ a haematological collection technician to accelerate the collection of malignant haematology samples. This has enabled our curator to focus on expanding the solid tumour collection. Since December 2010, when the Middlemore Tissue Bank was opened, we have collected samples from 201 donors, mostly blood cancer patients. Importantly, we have also begun collection of solid malignancies. Up to the end of June 2012 soft tissue sarcoma specimens from 18 patients have been collected with the help and enthusiasm of the orthopaedic surgeons. As of 30 June 2012 the tissue bank has a total of 3436 specimens stored in our freezers. Accompanying this growth has been the receipt of our first requests for the supply of tissue samples for use

in prospective research projects. We look forward to supporting clinical trials and clinical research projects requiring biospecimen collection and processing. The Middlemore Tissue Bank has worked to establish itself as part of the Australasian network of tissue banks that work collaboratively to make samples and data more accessible to researchers. We have developed close associations with the Australasian Leukaemia and Lymphoma Group (ALLG) Tissue Bank in Brisbane, Australia, the Victorian Cancer Biobank in Melbourne, and the Mayo Clinic in Rochester, US. Locally, we have presented at various scientific meetings to increase awareness and knowledge about the opportunities that tissue banking provides, as well as inviting future collaboration.

New specimens 2012

Increase over 2011

The last 12 months have been a period of steady growth culminating in the addition of a technician to our team to build further 900 on our strength in the haematological 800 collections. The beginning of solid tumour collection and completion of the 700 processes to supply tissues to researchers 600 means that we BIOSPECIMENS can soon look COLLECTED forward BY TYPE YEAR BY YEAR COMPARISON to receiving, and responding to, our first 500 application 900 for support.

BIOSPECIMENS COLLECTED BY TYPE YEAR BY YEAR COMPARISON

400

800

300

Dr Samar Issa FRACP, FRCPA 700 Founding Clinical Director Middlemore 600 Tissue Bank

200 100

500

0 11 12

400

11 12

300 200 100 0 11 12

11 12

Whatman FTA Spot Snap Frozen Tissue WBC Pellets EDTA Plasma Serum

CCREP ANNUAL REPORT - PAGE 21

MIDDLEMORE TISSUE BANK

CURATOR’S REPORT

183 30 18

Haematological Donors

The Collection 141 patients from Middlemore Hospital consented to make a tissue donation in the year ending 30 June 2012. This made the total number of donors 201, since the first consent was given on 16 December 2010. The majority of donors continue to be New Zealanders of european decent. Although the percentage of Maaori and Pacific donors remains less than the proportion that each group represents in the South Auckland population, it is pleasing to see the rate of consent has increased from the previous year. We continue to engage with Maaori and Pacific communities to further support them with their decisions concerning tissue donation. In the last year our haematological collection has grown steadily from 58 to 183 donors, representing 25 different malignancies. We anticipate a greater rate of growth in this collection next year (in both data and specimens), with the recent addition of a haematology collection technician to the team. The bone and soft tissue tumour collection has also grown from 2 to 18 donors in the same time period and represents 5 different types of sarcoma. Further expansion of the solid tumour collection is planned over the coming 12 months. Dried, whole, EDTA blood spots, preserved on Whatman FTA cards (suitable for genomic DNA extraction) has been added to the range of biospecimen types available. These are stored (along with serum and EDTA plasma) whenever matching blood specimens are available with solid tumour specimens, increasing the usefulness of such ‘sets’. Haematological malignancies continue to yield:

CCREP ANNUAL REPORT - PAGE 22

• • • •

white blood cell pellets (from bone marrow and peripheral blood) serum EDTA plasma snap frozen tissue

Summer Studentship A third summer studentship granted by CMDHB enabled us to appoint a student who evaluated a number of DNA and RNA extraction techniques on different biospecimen types. This work will assist us to expand the range and amount of biospecimens available to researchers.

Different Malignancies

Solid Tumours

Memberships The Middlemore Tissue Bank is a member of both the International Society for Biological and Environmental Repositories (ISBER) and the Australasian Biospecimen Network Association (ABNA). These memberships facilitate networking between biobanks worldwide, increasing opportunities for collaboration.

DONORS BY TUMOUR TYPE

Acknowledgments We are indebted to the following tissue banks for sharing their methodologies and experience: - Cancer Society Tissue Bank (Christchurch, NZ) - Neurological Society Brain Bank (Auckland, NZ) - Rare Disease Biobank (Otago, NZ) - Australasian Leukaemia and Lymphoma Group Tissue Bank (Brisbane, Australia) - Victorian Cancer Biobank (Melbourne, Australia) - Mayo Clinic 20K Tissue Bank (Minnesota, USA)

2011

2012

HAEMATOLOGICAL

DONORS BY ETHNICITY

NZ EUROPEAN MAAORI PACIFIC CHINESE INDIAN OTHER

SARCOMA

2012

DONORS BY ETHNICITY

2011

IN THE LAST YEAR OUR HAEMATOLOGICAL COLLECTION HAS GROWN STEADILY FROM 58 TO 125 DONORS, REPRESENTING 25 DIFFERENT MALIGNANCIES. CCREP ANNUAL REPORT - PAGE 23

10/100 1O years on, CCRep is involved with the conduct of over 100 clinical trials each year

2012 TRIAL ACTIVITY BY KEY RESEARCH AREA

CCREP ANNUAL REPORT - PAGE 24

0 3

PAEDIATRIC TRIAL ACTIVITY CCRep

CMDHB

Dianne Buskermolen (Community Health Worker) |Lyndsay Le Comte (Project Manager) Jean Leasi (Community Health Worker) Ruth Withers (Business Manager)

Kirstin Davey (Research Nurse) Emilina Jasmat (Research Nurse) Tania Knowles (Research Nurse) Shirley Lawrence (Research Nurse) Dr Adrian Trenholme (Investigator)

Many South Auckland children are disadvantaged with high rates of hospital admissions due to lower respiratory infections (LRIs) compared with national and international data. The research team at Kidz First Childrenâ&#x20AC;&#x2122;s Hospital have focussed their research efforts on looking at aspects of prevention (e.g. vaccine effectiveness) and also at models of intervention for children who present at the hospital with respiratory infections. The CCRep team work closely with the paediatric research staff at CMDHB to deliver high quality research outcomes. In the Healthy Lungs study a model of care

traditionally used in cystic fibrosis has been used to assess whether such a care model has an impact on the progression of respiratory illnesses in children from South Auckland at high risk of LRI. This project received HRC funding, is managed by CCRep and was on track to achieve its recruitment target of 400 participants by October 2012.

Investigator Initiated INVESTIGATOR INITIATED SHIVERS HEALTHY LUNGS PROSPECTIVE EPI STUDY

CCREP ANNUAL REPORT - PAGE 25

CARDIOLOGY

16 2

TRIAL ACTIVITY

Sponsored Trials

Investigator Initiated

CCRep

CMDHB

Ruth Cammell (Research Nurse) Diane Caveney (Research Nurse) Yvonne Dunn (Business Manager) Pene Eadie (Research Nurse) Zuzana Gray (Research Nurse) Lynette Pearce (Research Nurse)

Dr Wil Harrison (Investigator) Dr Patrick Kay (Investigator) Dr Andrew Kerr (Investigator) Dr Mayanna Lund (Investigator) Dr Douglas Scott (Investigator) Dr Niels van Pelt (Investigator) Dr Selwyn Wong (Investigator)

Commercially-sponsored trials of both drugs and devices have generated results that have improved care for many cardiology patients. Recently, however, there has been an international decline in sponsored cardiology trial activity which has seen a smaller number of CMDHB patients benefiting from participation.

and international evidence that there are large gaps between what is recommended and actual patient management in clinical practice. Over the last year, Dr Andrew Kerr has driven a project to develop a feedback system from the pharmaceutical dispensing database to identify whether prescribed preventative cardiac medications have been dispensed to discharged patients. CCRep cardiology research staff played a key role in recruiting the 230 people for this pilot study. It is hoped that the results will allow the development of tailored adherence support for patients.

One of the key areas of interest for the cardiology team at CMDHB is the incidence of readmission following a prior acute coronary syndrome despite appropriate, evidence-based lifestyle and medical treatment. There is very strong national

CCREP ANNUAL REPORT - PAGE 26

COMMERCIAL

INVESTIGATOR INITIATED

IMPROVE-IT PEOPLE TRA 2°P-TIMI 50 Early Prevent Pilot TRA•CER NC20971 ENGAGE AF-TIMI 48 EXCELLA II STABILITY APPRAISE-2 PLATINUM BC22140 SOLID-TIMI 52 EVOLVE CARDIVA CHAMPION PALLAS DAPT STUDY CHAMPION PHOENIX

INTENSIVE CARE TRIAL ACTIVITY

COMMERCIAL

CCRep

CMDHB

Yvonne Dunn (Business Manager)

Dr Tony Williams (Investigator) Dr Nigel Rankin (Investigator) Dr Alex Kazemi (Investigator) Chantal Hogan (Research Nurse) Judi Tai (Research Nurse) Anna Tisley (Research Nurse)

Research in the Intensive Care Unit (ICU) has been going from strength to strength. Staff members have grown, and trials have come from the Australian and New Zealand Intensive Care Society (ANZICS) as well as commercial sponsors.

aimed at improving clinical practice or patient care. The well-resourced research team have recruited successfully into a number of these trials.

CCRep actively supports the ICU team to streamline processes, particularly for the more demanding commercial trials, which means that the team can concentrate on the conduct of the trials and treatment of patients within the unit. A considerable number of the ANZICS-initiated trials are

September 2012 saw the retirement of Dr Nigel Rankin and Judi Tai, two enduring members of the ICU research team, who have worked with CCRep since its inception.

INVESTIGATOR INITIATED

F1K-MC-EVDP EPN ZORO STATINS ARISE NEPHRO-PROTECT RE-FEEDING

2 5

Sponsored Trials

Investigator Initiated CCREP ANNUAL REPORT - PAGE 27

HAEMATOLOGY TRIAL ACTIVITY

10 5

Sponsored Trials

CCRep

CMDHB

Renee Coxon (Research Nurse) Yvonne Dunn (Business Manager) Ann-Marie Ford (Research Nurse) Chris Giffney (Research Nurse) Lyn Haycock (Research Nurse)

Dr Hilary Blacklock (Investigator) Dr Samar Issa (Investigator) Dr Sharon Jackson (Investigator) Dr Gordon Royal (Investigator)

Oncology research continues to be an active area for CCRep and CMDHB. The last year has seen an increase in the number of feasibility assessments for pharmaceutical trials in malignant haematology. Many of these trials provide patients with access to potentially life-saving treatments that otherwise may not be available in New Zealand.

The good working relationship between the CCRep haematology research team and Middlemore Haematology Day Ward staff is integral to the success of the studies. The logistics of trial activity are managed by CCRep staff, and administration of cytotoxic drugs is carried out by the expert staff in the Day Ward. This cooperation has enabled some very complex trials to recruit successfully and provide excellent care to a cohort of particularly unwell patients.

CCREP ANNUAL REPORT - PAGE 28

Investigator Initiated COMMERCIAL

INVESTIGATOR INITIATED

EXTEND CML9 EINSTEIN WATCH AND WAIT 1160.46 REV-LITE CONTINUUM ASPIRE MK-0683-088 HOVON BRIGHT HOUSAI CEP-18770 TELESTO V212-011

RENAL

TRIAL ACTIVITY

4 CCRep

CMDHB

Jenny Han (Research Coordinator) Lynda Mockett (Business Manager)

Dr Mark Marshall (Investigator) Dr David Voss (Investigator) Renal Technicians: Kishore Krishnamoorthy Celestine (Yardly) Rodrigues

Increases in the number of patients with end-stage renal disease requiring dialysis over the last decade has increased largely in parallel with the rising incidence of type 2 diabetes mellitus. These problems are of particular significance in those of Maaori or Pacific ethnicity who form a large proportion of patients at CMDHB.

The focus of renal research at CMDHB is on factors influencing morbidity and mortality in patients with chronic renal failure. During the last 12 months Dr Mark Marshall has been awarded Health Research Council (HRC) funding for a trial in patients undergoing haemodialysis. The CCRep renal team was instrumental in setting up this trial and provides ongoing support in recruiting the trial participants.

Investigator Initiated INVESTIGATOR INITIATED SOLID OTAGO RENAL BLOCADE FAVOURED

CCREP ANNUAL REPORT - PAGE 29

DIABETES TRIAL ACTIVITY

12 1

Sponsored Trials

CCRep

CMDHB

Dr John Baker (Investigator) Rose Clarke (Research Nurse) Julia Leary (Research Nurse) Patricia Loft (Research Coordinator) Pauline O’Brien (Research Nurse) Ruth Withers (Business Manager)

Dr Ajith Dissanayake (Investigator) Dr Ian Rosen (Investigator) Dr Renate Koops (Research Fellow)

South Auckland is the hub of New Zealand’s diabetes epidemic and CMDHB has a commitment to improve outcomes for this population. Research is an important component of this approach and this is recognised through the investigators having protected time for research activities.

The diabetes team at CCRep, led by Dr John Baker, works closely with the DHB clinicians to undertake a range of sponsored trials and investigatorinitiated projects. In 2011/12 highlights included the continuation and extension of the xenotransplantation trial for type 1 patients and obtaining grant funding for a study looking at metformin in kidney disease.

CCREP ANNUAL REPORT - PAGE 30

Investigator Initiated

COMMERCIAL

INVESTIGATOR INITIATED

RECORD DIABECELL® ENDURE TECOS BUP3029 EXAMINE CANVAS BI 1218.64 DIA3010 MK-0524A-133 MK-0524B-118 IMAGINE 2

BARIATRIC

GASTROENTEROLOGY / HEPATOLOGY TRIAL ACTIVITY CCRep

CMDHB

Melissa Exeter (Research Coordinator) Rhonda Litchfield (Research Nurse) Ruth Withers (Business Manager)

Dr Stephen Gerred (Investigator) Dr Ravinder Ogra (Investigator)

Sponsored Trials

CCRep

CMDHB

Jill Bell (Research Nurse) Gene Jeon (Research Nurse) Cecilia Tong (ROBUST Project Manager, Research Nurse) Lynda Mockett (Business Manager)

Dr Fiona Horwood (PI) Dr Stuart Jones (PI) Dr Conor Oâ&#x20AC;&#x2122;Dochartaigh (PI) Dr Conroy Wong (PI) Dr Elaine Yap (PI Dr Andy Veale (PI)

A s for many other areas of research

Both investigator-initiated and sponsored clinical trials are managed by the CCRep respiratory team. Highlights in 2011/2012 included the successful completion of the EMBRACE trial in patients with bronchiectasis and publication of the results in the highly-regarded medical journal, The Lancet. Furthermore, Dr Conroy Wong has secured funding from the Health Research Council (HRC) of New Zealand to evaluate the use of tiotropium bromide in bronchiectasis patients.

undertaken by CCRep, Maaori have a higher incidence of respiratory disease than other ethnic groups in New Zealand. The CMDHB respiratory team are committed to ensuring better health outcomes for all those affected by these debilitating conditions, and all physicians are actively involved in clinical research.

CCREP ANNUAL REPORT - PAGE 32

Investigator Initiated

COMMERCIAL

INVESTIGATOR INITIATED

BI 352.2046 MANNITOL III C38072/3082 COSTA

EMBRACE PROCALCITONIN OSAPH ROBUST (Tiotropium)

TRIAL INDEX

CCRep ACTIVITY 2011/2012

CARDIOLOGY COMMERCIAL MPROVE-IT. A study to establish the clinical benefit and safety of Vytorin (ezetimibe/simvastatin tablet) vs simvastatin monotherapy in high-risk subjects presenting with acute coronary syndrome. TRA 20P – TIMI 50. A study to evaluate the safety and efficacy of SCH 530348 in addition to standard of care in subjects with a history of atherosclerotic disease: thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events. TRA•CER. A study to evaluate the safety and efficacy of SCH 530348 in addition to standard of care in subjects with acute coronary syndrome: thrombin receptor antagonist for clinical event reduction in acute coronary syndrome. NC20971. A study of RO4607381 in stable CHD patients with recent acute coronary syndrome.

CARDIVA CHAMPION. Study to demonstrate the safety and performance of the Champion Vascular Closure System (The Cardiva Champion Closure Device Study).

BUP3029. A comparison of the efficacy and safety of transdermal buprenorphine (Norspan® [BTDS]) and placebo in patients with diabetic peripheral neuropathic pain.

GASTROENTEROLOGY

PALLAS. A trial to assess the clinical benefit of dronedarone 400mg BID on top of standard therapy in patients with permanent atrial fibrillation and additional risk factors.

EXAMINE. A study to evaluate cardiovascular outcomes following treatment with alogliptin in addition to standard of care in subjects with type 2 diabetes and acute coronary syndrome (SYR-322_402).

GS-US-174-0102. An evaluation of tenofavir DF versus adefovir dipivoxil for the treatment of presumed pre-core mutant chronic hepatitis B.

DAPT Study. A trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent or bare metal stent placement for the treatment of coronary artery lesions. CHAMPION PHOENIX. A clinical trial comparing cangrelor to clopidogrel standard of care therapy in subjects who require percutaneous coronary intervention. INVESTIGATOR INITIATED PEOPLE. Prospective evaluation of outcome in patients with heart failure with preserved left ventricular ejection fraction. Funding: HRC. EARLY PREVENT PILOT. Toward the systematic use of dispensing records to prevent treatment gaps early after acute coronary syndromes. Funding: NZ Heart Foundation.

ENGAGE AF-TIMI 48. A study for evaluation of efficacy and safety of du-176b versus warfarin in subjects with atrial fibrillation – effective anticoagulation with factor Xa next generation in atrial fibrillation. EXCELLA II. An evaluation of the elixir novolimus-eluting coronary stent system compared to the Medtronic endeavor zotarolimus-eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions. STABILITY. A study of darapladib versus placebo in subjects with chronic coronary heart disease to compare the incidence of major adverse cardiovascular events (MACE). APPRAISE-2. An evaluation of the safety and efficacy of apixaban in subjects with a recent acute coronary syndrome. PLATINUM. A trial to assess an everolimus-eluting coronary stent system (promus element™) for the treatment of up to two de novo coronary artery lesions. BC22140. Study to evaluate the potential of aleglitazar to reduce cardiovascular risk in patients with a recent acute coronary syndrome event and type 2 diabetes mellitus (Alecardio). SOLID-TIMI 52. Study of darapladib versus placebo in subjects following acute coronary syndrome to compare the incidence of major adverse cardiovascular events. EVOLVE. A trial to assess the safety and effectiveness of the SYNERGY everolimum-eluting platinum chromium coronary stent system for the treatment of atherosclerotic lesion(s).

CANVAS. A study of the effects of jnj28431754 on cardiovascular outcomes in adult subjects with type 2 diabetes mellitus. BI 1218.64. A study of linagliptin in drug naïve or previously treated type 2 diabetic patients with moderate to severe renal impairment and insufficient glycaemic control. DIA3010. A study to evaluate the efficacy, safety, and tolerability of canagliflozin compared with placebo in the treatment of older subjects with type 2 diabetes mellitus inadequately controlled on glucose lowering therapy.

COMMERCIAL RECORD. A long-term study in patients with type 2 diabetes mellitus, comparing the combination of rosiglitazone and either metformin or sulphonylurea with metformin plus sulphonylurea on cardiovascular endpoints and glycaemia. DIABECELL®. An investigation of the safety and effectiveness of DiaBecell® [immunoprotected (alginateencapsulated) porcine islets for xenotransplantation] in patients with type 1 diabetes mellitus. SYR-322_305 ENDURE A study to evaluate the durability of the efficacy and safety of alogliptin compared to glipizide when used in combination with metformin in subjects with type 2 diabetes. TECOS. A trial to evaluate cardiovascular outcomes after treatment with sitagliptin in patients with type 2 diabetes mellitus and inadequate glycemic control on mono or dual combination oral anti-hyperglycemic therapy.

COMMERCIAL

GS-US-174-0103. An evaluation of tenofovir DF versus adefovir dipivoxil for the treatment of HbeAg positive chronic hepatitis B. NAFLD MARVEL. A study of 40mg MitoQ and placebo for the treatment of participants with raised liver enzymes due to non-alcoholic fatty liver disease. ABS4986g. Study to evaluate the efficacy and safety of rhuMAb BETA7 in patients with moderate to severe ulcerative colitis.

MK-0524A-133. A study to evaluate the efficacy and safety of extended release (ER) niacin/laropiprant when added to ongoing lipid-modifying therapy in patients with primary hypercholesterolemia or mixed dyslipidemia. MK-0524B-118. A study to evaluate lipid-altering efficacy and safety of extended-release niacin/laropiprant/ simvastatin combination in patients with primary hypercholesterolemia or mixed dyslipidemia. IMAGINE 2. A comparison of LY2605541 versus insulin glargine as basal insulin treatment in combination with oral antihyperglycaemia medications in insulinnaïve patients with type 2 diabetes mellitus: a double-blind, randomized study.

DIABETES

HEPATOLOGY

INVESTIGATOR INITIATED BARIATRIC. A randomised trial of adjunction intensive psychological, dietary and cultural management versus standard guidelines-based care to maximise weight loss among high-risk subjects with type 2 diabetes mellitus and morbid obesity treated with bariatric surgery. Funding: CMDHB, HRC, CCRep, Middlemore Foundation.

HAEMATOLOGY COMMERCIAL EXTEND. An extension study of eltrombopag olamine (SB-497115GR) in adults, with idiopathic thrombocytopenic purpura previously enrolled in an eltrombopag study. EINSTEIN. Oral direct factor Xa inhibitor rivaroxaban in patients with acute symptomatic deep-vein thrombosis or pulmonary embolism. 1160.46. A study of the efficacy and safety of oral dabigatran etexilate compared to warfarin for 6 month treatment of acute symptomatic venous thromboembolism, following initial treatment with a parenteral anticoagulant approved for this indication. CONTINUUM. A study of the efficacy and safety of lenalidomide as maintenance therapy for patients with B-cell chronic lymphocytic leukemia following second line therapy. MK-0683-088. A study of vorinostat or placebo with bortezomib in patients with multiple myeloma. BRIGHT. A study of bendamustine hydrochloride and rituximab (BR) compared with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the first-line treatment of patients with advanced indolent non-Hodgkin’s lymphoma or mantle cell lymphoma.

CCREP ANNUAL REPORT - PAGE 33

HOKUSAI. A study for the evaluation of efficacy and safety of (LMW) heparin/ edoxaban versus (LMW) heparin/ warfarin in subjects with symptomatic deep-vein thrombosis and/or pulmonary embolism.

INVESTIGATOR INITIATED

INVESTIGATOR INTIATED

EPN. Early parenteral nutrition versus standard care in the critically ill patient: a level I randomised controlled trial. Funding: University of Sydney.

EMBRACE. Prophylactic azithromycin for bronchiectasis: a randomised, controlled trial. Funding: HRC.

CEP-18770. A study to determine the maximum tolerated dose and evaluate the safety and efficacy of CEP-18770 in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma phase 1/phase 2.

STATINS. A phase II randomised controlled trial of atorvastatin therapy in intensive care patients with severe sepsis. Funding: Monash University.

TELESTO. A trial of deferasirox in patients with myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload.

NEPHRO-PROTECT. Nephro-protective effects of L-amino acids in critically ill patients. Funding: University of Sydney.

V212-011. A trial to study the safety and efficacy of V212 in adult patients with solid tumor or hematologic malignancy.

ARISE. The Australasian Resuscitation in Sepsis Evaluation randomised trial. Funding: Monash University.

RE-FEEDING. Management of re-feeding syndrome in critical illness. Funding: University of Sydney.

INVESTIGATOR INITIATED CML9. A study in adult patients with newly diagnosed chronic-phase chronic myeloid leukaemia of initial intensified imatinib therapy and sequential dose escalation followed by treatment with nilotinib in suboptimal responders to determine the rate and duration of major molecular response. Funding: ALLG. WATCH AND WAIT. Trial of rituximab versus a watch-and-wait strategy in patients with advanced stage, asymptomatic, non-bulky follicular lymphoma. Funding: ALLG. Rev-Lite. Trial of low dose lenalidomide and dexamethasone in relapsed or refractory multiple myeloma in patients at high risk for myelosuppression. Funding: Peter MacCallum Cancer Centre.

PAEDIATRIC INVESTIGATOR INITIATED PROSPECTIVE EPI STUDY - Impact of pneumococcal vaccine on hospital admission in children with pneumonia. Funding: HRC

ASPIRE. A trial examining the efficacy and safety of low-dose aspirin after initial oral anticoagulation to prevent recurrent venous thromboembolism. Funding: University of Sydney.

HEALTHY LUNGS - A randomised control trial of an intervention programme based on the cystic fibrosis model of care in children less than two years of age admitted to hospital with severe lower respiratory tract infection to prevent chronic lung disease. Funding: HRC

HOVON. Rituximab in primary central nervous system lymphoma (PCNSL): a randomized HOVON/ALLG intergroup study. Funding: ALLG.

SHIVERS: Southern Hemisphere Influenza Vaccine Effectiveness Research and Surveillance. Funding: US Centres for Disease Control

RENAL INVESTIGATOR INITIATED SOLID. A trial of low sodium dialysate versus conventional sodium dialysate to reduce left ventricular mass index in patients receiving home haemodialysis: The SOdium Lowering In Dialysate trial. Funding: HRC.

BLOCADE. The Beta-blocker to LOwer CArdiovascular Dialysis Events Feasibility Study to find the benefits of treating patients with end-stage kidney disease requiring dialysis, with the drug carvedilol, and to work out their risk of side effects. Funding: Australian Kidney Trial Network sub-contract. FAVOURED. A trial to assess the effect of aspirin and fish oil (omega-3 fatty acids) in the prevention of early thrombosis in arterio-venous fistulae in patients with Stage IV or V chronic kidney disease requiring haemodialysis. Funding: Australian Kidney Trial Network subcontract.

F1K-MC-EVDP. A study of drotrecogin alfa (activated) administered as a continuous 96-hour infusion to adult patients with septic shock. ZORO. A study to evaluate the efficacy and safety of intravenous zanamivir twice daily compared to oral oseltamivir twice daily in the treatment of hospitalized adults and adolescents with influenza.

CCREP ANNUAL REPORT - PAGE 34

ROBUST (Tiotropium). A multi-centre, double-blind, randomised, placebocontrolled, crossover trial of tiotropium treatment in adult patients with stable, non-cystic fibrosis bronchiectasis. Funding: HRC.

RHEUMATOLOGY COMMERCIAL WA16855. Study of the efficacy and safety of re-treatments with rituximab (Mabthera®) in patients with active rheumatoid arthritis. GOLIMUMAB T05. A trial of golimumab, a fully human anti-TNFa monoclonal antibody, administered subcutaneously, in methotrexate-naïve subjects with active rheumatoid arthritis. CNT01275PSA3001. A trial of ustekinumab, an fully human anitIL-12/23p40 monoclonal antibody, administered subcutaneously, in subjects with active psoriatic arthritis.

COMMERCIAL

OSAPH. Obstructive Sleep Apnoea in Pregnancy Hypertension. Funding: HRC.

OTAGO RENAL. Longitudinal survey of health-related quality of life outcomes for individuals aged ≥65 years on, or eligible for, dialysis therapy and survival outcomes. Funding: HRC sub-contract.

RESPIRATORY

INTENSIVE CARE

PROCALCITONIN. The clinical utility of sputum procalcitonin, a novel marker of bacterial infection, in bronchiectasis. Funding: Auckland Medical Research Foundation.

BI 352.2046. A study to evaluate the impact of stepwise withdrawal of inhaled corticosteroid treatment in patients with severe to very severe chronic obstructive pulmonary disease on optimised bronchodilator therapy. MANNITOL III. A study to investigate the safety and efficacy of inhaled mannitol over 12 months in the treatment of bronchiectasis. C38072/3082. A study to evaluate the efficacy and safety of Reslizumab (3.0 mg/kg) in the reduction of clinical asthma exacerbations and change in lung function in patients (12-75 years of age) with eosinophilic asthma. COSTA. A study to evaluate the efficacy, safety and dosing regimens of MEMP1972A in adults with allergic asthma who are inadequately controlled on inhaled corticosteroids and a second controller.

WA22762. A study of the safety and effect on clinical outcome of tocilizumab SC versus tocilizumab IV, in combination with traditional disease modifying anti-rheumatoid arthritis drugs, in patients with moderate to severe active rheumatoid arthritis. H9B-MC-BCDT. A study to evaluate the efficacy and safety of subcutaneous LY2127399 in patients with systemic lupus erythematosus (ILLUMINATE). PALACE-1. A study of two doses of apremilast (CC-10004) in subjects with active psoriatic arthritis. LASSO 401. Long-term allopurinol safety study evaluating outcomes in gout patients. RDEA594-302. Study to evaluate the efficacy and safety of lesinurad and allopurinol compared to allopurinol alone in subjects with gout who have had an inadequate hypouricemic response to standard of care allopurinol (CLEAR 2). DUAL-2. Study to assess the efficacy, safety and tolerability of macitentan in patients with ischemic digital ulcers associated with systemic sclerosis.

Financial Reports

2012

CCREP ANNUAL REPORT - PAGE 35

APPROVAL BY TRUSTEES

FINANCIAL STATEMENTS For the year ended 30 June 2012

Approval By Trustees

The Trustees have approved the Financial Statements of Clinical Research and Effective Practice Foundation for the year ended June 30, 2012 on pages 37 to 45.

For and on behalf of the Trustees .

CCREP ANNUAL REPORT - PAGE 36

Trustee

Date

NOTES TO THE STATEMENT OF

FINANCIAL STATEMENTS ACCOUNTING POLICIES For the year ended 30 June 2012

1. Reporting Entity

Grants (Support Funding)

The Clinical Research and effective practice Foundation (CCRep) was established in 2001 as a charitable trust whose key objectives are to undertake, conduct and promote clinical research, evidence-based practice and educational initiatives within the South Auckland region.

Grants received are recognised as revenue when the requirements under the grant agreement have been met. Any grants for which the requirements under the grant agreement have not been completed are carried as liabilities (revenue in advance) until all the conditions have been fulfilled.

CCRep is a charitable trust registered under the Charities Act 2005.

Interest income

2. Basis for Preparation The financial statements have been prepared on the historical cost basis. The reporting currency is New Zealand dollars.

3. Specific Accounting Policies The specific accounting policies used in the preparation of the financial statements are as follows.

3.1 Revenue Services in relation to Managed Research Funds

Projects in progress are classified as Managed Research Funds, with amounts received and paid out on behalf of these projects shown as Contract Income and Expenditure in the Statement of Financial Performance. The fee receivable by CCRep for the management of these funds is recognised as income in the Statement of Financial Performance in the accounting period in which the services are provided. Amounts received from customers in advance of the services being provided are carried as liabilities (revenue in advance). Services in relation to Specific Funds

On completion of projects, any surplus remaining and attributable to the PI (Principal Investigator) are transferred into the Specific Funds balance. Amounts received and paid out on behalf of these funds by CCRep are shown in the movement in Specific Funds and are not included in the Statement of Financial Performance. The fee receivable by CCRep for the management of the funds is recognised as income in the Statement of Financial Performance.

Interest income is recognised on an accruals basis.

3.2 GST The Financial Statements have been prepared using GST exclusive figures with the exception of debtors and creditors which are stated GST inclusive.

3.3 Foreign Currency Transactions Transactions denominated in foreign currencies are translated into the reporting currency using the exchange rate in effect at the transaction date. Monetary items receivable or payable in a foreign currency, other than those resulting from short-term transactions covered by forward exchange contracts, are translated at balance date at the closing rate. For transactions covered by short-term forward exchange contracts, the rates specified in those contracts are used as the basis for measuring and reporting the transaction. Exchange differences on foreign currency balances are recognised in the Statement of Financial Performance.

3.4 Taxation CCRep has been granted charitable status under the Income Tax Act by the Inland Revenue Department; hence it is exempt from income tax. CCRep was reregistered as a charitable entity under the Charities Act 2005 on 4 March 2008.

3.5 Debtors Debtors are stated at estimated realisable value after providing against debts where collection is doubtful.

3.6 Property, Plant & Equipment Property, plant and equipment are recorded on the historical cost basis. Provision is made for any permanent impairment in the value of property, plant and equipment.

CCREP ANNUAL REPORT - PAGE 37

NOTES TO THE STATEMENT OF

FINANCIAL STATEMENTS ACCOUNTING POLICIES For the year ended 30 June 2012

All items of property, plant and equipment are depreciated on a straight line basis at rates that will write off their cost less estimated residual value over their expected useful lives. Depreciation rates used: Clinical Equipment 15.5% - 18.0% Information Technology 30.0% Other Equipment 10.0% - 24.0%

3.7 Specific and Managed Research Funds Managed Research Funds

Managed Research Funds are those projects in progress managed by CCRep. The balance on these funds is recognised as a liability as it is only available to be used for the benefit of the PI in accordance with specific restrictions imposed by the fund agreement.

3.9 Impairment Annually the trustees assess the carrying value of each asset. Where the estimated recoverable amount of the asset is less than its carrying amount, the asset is written down. The impairment loss is recognised in the statement of financial performance.

3.10 Employee entitlements Employee entitlements to salaries and wages, annual leave and other benefits are recognised when they accrue to employees. The liability for employee entitlements is carried at the present value of the estimated future cash outflows.

3.11 Financial Instruments

On completion of projects, any surplus remaining and attributable to the Principal Investigator (PI) is transferred into the Specific Funds balance.

CCRep uses various financial instruments with off-balance sheet risk for the primary purpose of reducing its exposure to fluctuations in foreign currency exchange rates and interest rates. While these financial instruments are subject to risk that market rates may change subsequent to acquisition, such changes would generally be offset by opposite effects on the items being hedged.

In addition, Specific Funds are also initiated when funding or donations are received by a PI, the cash funds are transferred to CCRep to be held on behalf of the PI but CCRep has no direct involvement in managing the projects to be undertaken with that funding.

“ Forward exchange contracts entered into as hedges of foreign exchange assets or liabilities are valued at the exchange rates prevailing at transaction time. Any unrealised gains or losses are offset against foreign exchange gains or losses on the related asset or liability. “

These funds are to be used in accordance with specific restrictions imposed by the fund agreement. CCRep manage and administer the cash funds. The notes to the financial statements provide a breakdown of the balance held by project and a reconciliation of the movement in funds in the period.

3.12 Differential Reporting

Specific Funds

3.8 Reserves Retained earnings

Retained earnings are unrestricted funds which are available for use at the discretion of the Trustees in furtherance of the objectives of the Foundation and which have not been designated for other purposes. Designated funds

Designated funds are unrestricted funds which have been reserved by the Trustees for a specific purpose. The aim and use of the designated funds is set out in Note 6 to the financial statements

CCREP ANNUAL REPORT - PAGE 38

CCRep qualifies as a differential reporting entity as it has no “public accountability” and it is small in that the total assets are less than $10 million and total revenue is less than $20 million. CCRep has taken advantage of all differential reporting exemptions with the exception that it has complied with FRS19, accounting for goods and services tax. The financial statements have been prepared in accordance with New Zealand generally accepted accounting practice. The financial report is a general-purpose financial report, which has been prepared recognising the framework for differential reporting by the New Zealand Institute of Chartered Accountants.

4.0 Changes in Accounting Policies There have been no changes in accounting policies during the period.

NOTES TO THE STATEMENT OF

FINANCIAL STATEMENTS PERFORMANCE

June

For the year ended 30 June 2012

($)

INCOME Contracts Income 3,888,585 3,754,870 Expenditure 2,585,685 2,439,021

Contract Margin

1,302,900

1,315,849

PI Share of Contract Margin

437,758

442,666

Contracts Net Surplus

865,142

873,183

Administration Revenue CMDHB Support Funding 350,000 350,000 Interest Receivable 124,759 119,298 Managed Fund Fees 98,711 82,121 Gain on Foreign Exchange 31,895 47,810 Other Income 62,736 54,359

Total Net Income

1,533,243

1,526,771

Administration Expenditure Wages & Salaries 908,171 846,056 Outsourced Personnel 33,382 32,631 IT Systems/Telecommunications 74,296 36,811 Insurance 25,444 18,000 Audit Fees 14,550 11,200 Legal Fees 6,585 4,485 Printing & Stationery 18,450 15,735 Depreciation 31,049 22,806 Staff travel and accommodation 44,053 27,677 Communications 11,689 10,261 Misc Others 88,560 173,217

Total Administration Expenditure

Net Surplus

1,256,229

1,198,879

277,014

327,892

STATEMENT OF

MOVEMENTS IN RESERVES

Total Reserves at Beginning of the Year Net Surplus for the Year Transferred to Specific Funds

Reserves at the end of the Year

June

For the year ended 30 June 2012

($)

1,616,754 277,014 -

1,288,862 327,892 -

1,893,768

1,616,754

CCREP ANNUAL REPORT - PAGE 39

STATEMENT NOTES TO THE OF

FINANCIAL POSITION STATEMENTS

June

As Foratthe 30 year Juneended 2012 30 June 2012

Note

($)

ASSETS Current Assets ASB General Bank 165,747 230,991 Petty Cash 500 500 Term Investments and Forex 1 5,865,923 5,283,240 Debtors 2 1,885,135 1,666,626 Prepayments 37,045 32,687

Total Current Assets

7,954,350

7,214,044

Non Current Assets Property, Plant & Equipment 3 74,949 80,593 Total Assets

74,949

80,593

8,029,299

7,294,637

LIABILITIES Current Liabilities Creditors 4 Specific Funds 5 Revenue in Advance GST Payable

Total Current Liabilities

372,024 4,860,472 841,143 61,892 6,135,531

376,761 4,577,216 613,412 110,494 5,677,883

Net Assets

1,893,768

1,616,754

Represented by: Reserves Capitalised Trust Funds 100 100 Designated Funds 6 30,000 30,000 Retained Earnings 6 1,863,668 1,586,654

Total Reserves

1,893,768

1,616,754

These Financial Statements should be read in conjunction with the accounting policies on pages 37 to 38 and the notes on pages 41 to 45. CCREP ANNUAL REPORT - PAGE 40

NOTES TO THE

FINANCIAL STATEMENTS For the year ended 30 June 2012

1 Term Investment & Forex Accounts

Jun-12 $

Maturity Date

Weighted Rate %

June

Jun-11 $

Maturity Date

Weighted Rate %

June

2 Debtors

June

‘61’ Money Market a/c 8,669 On Call 0.75% 75,396 On Call 0.75% ‘50’ Money Market a/c 272,904 On Call 3.15% 50,124 On Call 3.15% Term deposits < 12 months-ASB 2,400,000 < 1 year 4.66% 2,000,000 < 1 year 5.21% > 12 months-ASB - > 1 year 0.00% 250,000 > 1 year 4.95% < 12 months-ANZ 600,000 < 1 year 4.99% 450,000 < 1 year 5.31% > 12 months-ANZ 1,800,000 > 1 year 5.54% 1,700,000 > 1 year 5.73% > 12 months-ANZ 500,000 Perpetual 9.66% 500,000 Perpetual 9.66% $USD 240,776 On Call 0.00% 134,330 On Call 0.00% $GBP 43,574 On Call 0.00% 39,502 On Call 0.00% $AUD - On Call 1.50% 83,888 On Call 2.10% Total 5,865,923 5,283,240

Trade receivables Accrued Income Interest income accrued

1,095,948 686,012 103,175 1,885,135

1,054,296 508,689 103,641 1,666,626

3 Property, Plant and Equipment June 2012 Item Cost Depreciation $ $

Clinical Equipment 146,222 Office Equipment 18,962 Information Technology 122,408 287,592

Accumulated Depreciation $

Net Book Value $

17,434 107,100 39,122 1,841 9,220 9,742 19,222 96,323 26,085 38,497 212,643 74,949

Property, Plant and Equipment June 2011

Item Cost Depreciation $ $

Clinical Equipment 141,456 Office Equipment 18,962 Information Technology 94,320 254,738

Accumulated Depreciation $

19,061 89,665 1,242 7,379 9,833 77,101 30,136 174,145

Net Book Value $

51,791 11,583 17,219 80,593

CCREP ANNUAL REPORT - PAGE 41

NOTES TO THE

FINANCIAL STATEMENTS

June

For the year ended 30 June 2012

4 Creditors

Trade Creditors - CMDHB Accruals Employee entitlements

5 (a) Specific Funds

23,878 90,798 257,348

32,902 126,112 217,747

372,024

376,761

191,052 225,578 79,573 9,000 76,845 7,539 42,090 272,950 161,299 520 112,589 275,889 8,245 6,108 951,916 286,750 131,302 - 7,285 1,211 98,245 4,292 9,889 5,445 - 12,915 - 141,313 - 255 84,930 2,063 1,907 49,840 527 17,008 32,427 866 7,306 15,107 3,147 34,467

194,529 181,178 123,995 9,000 89,782 7,608 127,990 299,693 152,741 26 83,508 438,019 8,275 6,255 837,962 113,211 124,632 53 8,096 1,629 104,469 4,292 1,908 110 12,244 5,629 135 140,250 24,846 686 63,781 2,434 1,802 3,811 946 9,692 -

Ideal Respiratory GMMH Mira Szaszy Taranaki Sharp Stroke Outcomes Diabetes Fund MM Hepatitis Research Fund CMDHB Rheumatology Research Fuzzy Neural System NICE Study Fund KidzFirst Research Development Diabetes Project Trust/Research Fellow Evaluation of Group Education Cardiology Fund Haematology Research & Spec Purposes Cardiology Capex Fund Spironolactone in ESKD Obstetric Ultrasound Research Integrated Care Flu Study Fund LJ - COTTS Study CMDHB Research Officer Endocrinology Education Fund Breast Carcinoma - FISH study Colorectal Cancer Postnatal Depression Innovation fund Kok Fresenius CIU Education Fund Middlemore Tissue Bank Disabled by Illness or Injury : Does it Matter? Div Med Science Symposium Kidz First Neonatal Research Serotyping of Streptococcus Microbiology S Taylor stipends Hand and Upper Limb Xeno Hill Fund Smoking Cessation amongst Junior Doctors Cardiac Cath Lab Nurses Education Fund Dermatology Research Fund Cure Kids SUDI Study

Specific Fund balance

CCREP ANNUAL REPORT - PAGE 42

3,369,690

3,185,217

NOTES TO THE

FINANCIAL STATEMENTS

5 (a) Specific Funds - Continued

June

For the year ended 30 June 2012

Movement in Specific Funds during the year: Opening balance 3,185,217 3,061,479 Income received on behalf of the Specific Funds 931,623 814,001 Payments made on behalf of the Specific Funds (990,503) (948,196) Completed projects transferred from Managed Research Funds 338,975 339,234 Transferred from Designated Funds - CC Rep management fees (95,622) (81,301)

Sub Total: Completed Projects

3,369,690

3,185,217

5 (b) Managed Research Funds

Provisional amounts in relation to projects in progress Less: amounts transferred to Specific Funds upon project completion

Sub Total: Projects in progress

June

Total

1,859,757

1,761,233

(338,975)

(339,234)

1,520,782

1,421,999

Less: Innovation Fund in designated Funds per note 6b (30,000)

June

4,860,472

(30,000) 4,577,216

The balances held on Specific Funds and Managed Research Funds are to be used by the investigators in accordance with specific restrictions imposed by the fund agreement, typically in the furtherance of research and research related activities including education and conference attendance, materials, assets and related assistance.

CCREP ANNUAL REPORT - PAGE 43

NOTES TO THE

FINANCIAL STATEMENTS

June

For the year ended 30 June 2012

6 Reserves

6 (a) Retained Earnings

Opening Balance Net Surplus for the Year Transfer to Designated Funds

Closing Balance

1,586,654 277,014 - 1,863,668

1,258,762 327,892 - 1,586,654

6 (b) Designated Funds

Opening Balance 30,000 30,000 Transferred from Retained Earnings - - Transferred to Specific Funds - -

Closing Balance

30,000

Amounts are transferred out of retained earnings into designated funds when the Trustees commit to making a contribution to the Innovation Fund, subject to the identification and approval of projects for which this funding will be used. The funding is subsequently transferred from the designated fund to the specific fund (see note 5(a)) at the time that projects are identified and approved.

7. Contingent Liabilities

There were no known contingent liabilities as at 30 June 2012 (2011: nil).

8. Commitments 8 (a) Capital Commitments

There were no known capital commitments as at 30 June 2012 (2011: nil).

CCREP ANNUAL REPORT - PAGE 44

NOTES TO THE

FINANCIAL STATEMENTS

June

8 (b) Operating Lease Commitments

June

For the year ended 30 June 2012

Operating Lease Commitments

Within one Year Later than one year but no longer than five years Later than five years

9,243 8,472 -

9,243 17,715 -

17,715

26,958

CCRep leases plant and equipment. There are no options to purchase in respect of plant and equipment held under operating leases. There are no sub leases from the above.

9. Related Parties

The Counties Manukau District Health Board (CMDHB) provides funding to CCRep which is disclosed separately in the statement of financial performance. The CMDHB also supplies the premises at no charge and makes purchases on CCRep’s behalf. These purchases are expensed or capitalised in CCRep’s financial statements as appropriate and the balance owing is disclosed in Note 4.

10. International Financial Reporting Standards (IFRS) CCRep has chosen not to adopt the New Zealand Equivalents to International Financial Reporting Standards (“NZ IFRS”). The decision not to adopt is consistent with the exemption provided by the Accounting Standards Review Board (“ASRB”) Release 9, issued in September 2007. ASRB Release 9 provides a choice to certain qualifying entities to either adopt NZ IFRS or to continue to apply New Zealand Financial Reporting Standards (“NZ FRS”). CCRep is a qualifying entity on the basis that it is not an issuer, is not required to file financial statements with the Registrar of Companies under section 19 of the Financial Reporting Act 1993 and is not considered large (less than $20m revenue and less than $10m total assets).

CCREP ANNUAL REPORT - PAGE 45

Independent Auditors’ Report to the Trustees of the Clinical Research and Effective Practice Foundation Report on the Financial Statements We have audited the financial statements of the Clinical Research and Effective Practice Foundation on pages 37-45, which comprise the statement of financial position as at 30 June 2012, the statement of financial performance and statement of movement in reserves for the year then ended, and the notes to the financial statements that include a summary of significant accounting policies and other explanatory information. Trustees Responsibility for the Financial Statements The Trustees are responsible for the preparation and fair presentation of financial statements in accordance with generally accepted accounting practice in New Zealand and for such internal controls as the Trustees determine are necessary to enable the preparation of financial statements that are free from material misstatement, whether due to fraud or error. Auditors’ Responsibility Our responsibility is to express an opinion on these financial statements based on our audit. We conducted our audit in accordance with International Standards on Auditing (New Zealand) and International Standards on Auditing. These standards require that we comply with relevant ethical requirements and plan and perform the audit to obtain reasonable assurance about whether the financial statements are free from material misstatement. An audit involves performing procedures to obtain audit evidence about the amounts and disclosures in the financial statements. The procedures selected depend on the auditors’ judgement, including the assessment of the risks of material misstatement of the financial statements, whether due to fraud or error. In making those risk assessments, the auditors consider the internal controls relevant to the entity’s preparation of financial statements that present fairly the matters to which they relate, in order to design audit procedures that are appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the entity’s internal control. An audit also includes evaluating the appropriateness of accounting policies used and the reasonableness of accounting estimates, as well as evaluating the overall presentation of the financial statements. We believe that the audit evidence we have obtained is sufficient and appropriate to provide a basis for our audit opinion. Other than in our capacity as auditors we have no relationship with, or interests in, the Clinical Research and Effective Practice Foundation.

CCREP ANNUAL REPORT - PAGE 46

Independent Auditors’ Report Clinical Research and Effective Practice Foundation Opinion In our opinion, the financial statements on pages 37 to 45 present fairly, in all material respects, the financial position of the entity as at 30 June 2012, and its financial performance for the year ended on that date in accordance with generally accepted accounting practice in New Zealand. Restriction of Distribution or Use This report is made solely to the entity’s Trustees, as a body. Our audit work has been undertaken so that we might state to the entity’s Trustees those matters which we are required to state to them in an auditors’ report and for no other purpose. To the fullest extent permitted by law, we do not accept or assume responsibility to anyone other than the entity and the entity’s Trustees, as a body, for our audit work, for this report or for the opinions we have formed.

Chartered Accountants Auckland 30 October 2012

CCREP ANNUAL REPORT - PAGE 47