CLINICAL RESEARCH IN AUSTRALIA

CLINICAL RESEARCH IN AUSTRALIA

NHMRC Clinical Research Working Group report 1 CLINICAL RESEARCH IN AUSTRALIA REPORT OF THE NHMRC CLINICAL RESEARCH WORKING GROUP November 2001

NHMRC Clinical Research Working Group report 2 Contents Membership of the Clinical Research Working Group 5 Foreword 7 Principal recommendations 8 1 Introduction 13 1.1 Why the Working Group was established 1.2 Terms of reference 1.3 Definition of ‘clinical research’ 1.4 What the Working Group did 2 Current status of clinical research in Australia 17 2.1 Preamble 2.2 Main sources of funding 2.3 Information on clinical research activity 2.4 Information on support for clinical research 2.5 Specific recommendations 3 Clinical research training 24 3.1 Scope of clinical research training 3.2 Training expectations and needs of clinicians entering clinical research 3.3 Training program structures and curricula 3.4 Funding of clinical-research training 3.5 Specific recommendations 4 Maintaining clinical research capacity 35 4.1 Preamble 4.2 Proposal for a Clinical Practice Research Development Scheme 4.3 NHMRC clinical-research assessment processes 4.4 Clinical trials and large-scale patient-recruitment research 4.5 Clinical trials centres 4.6 Centres of Clinical Excellence 4.7 Office of the NHMRC 4.8 Specific recommendations 5 Repositories for clinical research 51 5.1 Tissue banks 5.2 Disease registers 5.3 Registers of clinical trials 5.4 Specific recommendations Appendix 1: Consultation of the health and medical research community 58 Appendix 2: Examples of clinical research initiatives undertaken 66 by professional organisations References 72

NHMRC Clinical Research Working Group report 3 NHMRC Clinical Research Working Group Membership Professor Lawrie Beilin Head, Department of Medicine University of Western Australia Royal Perth Hospital Professor Judy Black NHMRC Senior Principal Research Fellow Department of Pharmacology University of Sydney Professor John Chalmers (chair) Chair, Research Development Faculty of Medicine University of Sydney Professor Chris Del Mar Director, Centre for General Practice University of Queensland Professor Paul O’Brien Head, Department of Surgery Monash University The Alfred Hospital, Melbourne Professor Don Roberton Head, Department of Paediatrics University of Adelaide Women’s and Children’s Hospital, Adelaide Professor Tania Sorrell Professor of Clinical Infectious Diseases Deputy Head, Department of Medicine University of Sydney Associate Professor Robyn Ward Department of Medical Oncology University of New South Wales St Vincent’s Hospital, Sydney Professor John Zalcberg Director, Division of Haematology and Medical Oncology Peter MacCallum Cancer Institute University of Melbourne

NHMRC Clinical Research Working Group report 4 Secretariat Ms Elizabeth Hoole, Office of NHMRC Ms Wendy Fahy, Office of NHMRC Reporter Associate Professor Michael Frommer Deputy Director, Effective Healthcare Australia Sub-Dean (Research) School of Population Health and Health Service Research University of Sydney This report was prepared by: Michael Frommer John Chalmers Lucie Rychetnik

NHMRC Clinical Research Working Group report 5 Foreword In commissioning the Clinical Research Working Group, the National Health and Medical Research Council emphasised that its deliberations would represent the first phase in a broader continuing program of inquiry into clinical research in Australia. The Working Group was required to limit its consideration of workforce development to issues affecting medical graduates, as the NHMRC intended to establish other working groups to examine issues affecting other professional disciplines. Therefore, in accordance with its terms of reference and the specific instructions received from the NHMRC, the Working Group restricted its consideration of clinical research workforce development, training and career structures to issues affecting medical graduates.

The Working Group conducted a very broadly-based e-mail survey of issues relevant to clinical research. The survey was distributed to researchers from all disciplines and to all other individuals on the NHMRC e-mail list server. The Working Group also sought opinions and information from a wide range of professional, academic and government bodies involved in the training, employment and career structure of medical graduates participating in clinical research. The Working Group did not consult with analogous bodies involved in the training and career development of other health professionals participating in clinical research. It was foreshadowed that such consulation would be undertaken by a new working group set up specifically for the purpose in a second phase.

NHMRC Clinical Research Working Group report 6 Principal recommendations Recommendations in this report comprise principal recommendations 1-21, given below, and specific recommendations, given at the end of Chapters 2-5. Principal recommendations 1-2: Leadership role of the NHMRC Recommendation 1 The NHMRC should take a leadership role in the enhancement, development and support of clinical research programs, capacity and infrastructure in Australia. The Office of the NHMRC should appoint a full-time clinical academic to implement this leadership role (see Recommendation 20).

Recommendation 2 Through its leadership role, the NHMRC should resolve the current paradox whereby governments, health authorities and universities promote evidence-based practice and acknowledge the importance of clinical research that generates the evidence, but impose service workloads that prevent talented researchers from pursuing clinical research. Principal recommendation 3: Contribution of clinical research to evidence-based practice and improvements in the safety and quality of health services Recommendation 3 Through its leadership role, the NHMRC, in partnership with other agencies, should ensure support for clinical research that underpins the development of evidence-based practice and improvements in the safety and quality of health services. Principal recommendations 4-6: Partnerships and alliances Recommendation 4 The NHMRC should recognise that the enhancement, development and support of clinical research will require collaboration, cooperation and partnerships with and between Commonwealth, State and Territory governments (especially departments of health and education), health authorities and health services, universities, professional colleges and societies, and research agencies and foundations.

Recommendation 5 The NHMRC should recognise the crucial role of academic health services in supporting or potentially supporting clinical research. The NHMRC should seek collaborations with these health services (which include teaching hospitals and non-

NHMRC Clinical Research Working Group report 7 hospital academic clinical units) to enhance the development and support of clinical research. Recommendation 6 In supporting the development of clinical research, the NHMRC should seek to work with and through existing national, State and Territory bodies such as the National Institute of Clinical Studies, the Australian Council for Safety and Quality in Health Care, and the NSW Medical Training and Education Council. The NHMRC should encourage and facilitate the formation of similar bodies in States and Territories where these do not already exist.

Principal recommendation 7: Monitoring the status of clinical research in Australia Recommendation 7 The NHMRC should formulate criteria for classifying research-grant applications as ‘clinical’ or ‘non-clinical’, and should develop mechanisms for monitoring the extent and quality of clinical research and the capacity for clinical research in Australia. Other agencies that fund clinical research in Australia should be encouraged to use the same criteria. Principal recommendation 8: Clinical research workforce development, training and career structures for non-medical graduates Recommendation 8 The NHMRC should establish further working groups to examine clinical research workforce development, training and career structures for non-medical graduates. Principal recommendations 9-12: Commitment to developing and maintaining the clinical-research workforce and capacity Recommendation 9 The NHMRC should take responsibility for improving and coordinating the recruitment of well-trained and talented clinical researchers, and for their retention in the research workforce.

Recommendation 10 The NHMRC should take responsibility for improving and coordinating the training of clinical researchers, recognising that this requires cooperation of many organisations that each play important but segmented roles, including universities, professional colleges and societies, health services and hospital authorities, and governments.

NHMRC Clinical Research Working Group report 8 Recommendation 11 NHMRC-funded clinical trials centres, Centres of Clinical Excellence, recipients of NHMRC program grants for clinical research, and recipients of substantial NHMRC funding for other initiatives connected with clinical research, should be required to support the training of clinical researchers and the mentoring of clinical research trainees. Recommendation 12 The NHMRC should initiate and contribute to a national Clinical Practice Research and Development scheme, with the aim of increasing the recruitment and retention of clinician researchers in the research workforce through the progressive introduction and development of positions providing protected research time in clinical centres for fully-fledged, well-trained clinical researchers.

Principal recommendations 13-14: Enhancing the assessment of clinical research funding applications by the NHMRC Recommendation 13 The NHMRC should establish a Grants Review Panel (GRP) to assess grant applications for clinical trials and other large-scale patient-recruitment (CTLS) research. The functions of this GRP should be similar to the functions of other GRPs (or discipline panels). Like other GRPs, it should make direct recommendations for funding of research proposals. Recommendation 14 The NHMRC should substantially strengthen the clinical-research expertise represented in a number of GRPs, so that these GRPs can make balanced, well- informed assessments of the majority of applications for funding of clinical research projects.

Principal recommendations 15-16: Support of clinical trials centres and networks, and support of Centres of Clinical Excellence Recommendation 15 The NHMRC should continue, and enhance, existing programs that support clinical trials centres, and should initiate support for clinical trials networks and other collaborative clinical-research networks. Recommendation 16 The NHMRC should continue, and enhance, existing programs that support Centres of Clinical Excellence in Hospital-Based Research.

NHMRC Clinical Research Working Group report 9 Principal recommendations 17-18: Development of human tissue banks and disease registers Recommendation 17 The NHMRC should take a leadership role in a national approach to the development of human tissue banks, and should convene a regular forum to make recommendations on standardised procedures for the management and operation of tissue banks. This forum should report to the Research Committee. Recommendation 18 The NHMRC Research Committee should take a leadership role in promoting the development of disease registers, particularly clinic- and hospital-based registers. The Research Committee should sponsor a regular national forum for methodological development of disease registers, including linkages between tissue banks and disease registers.

Principal recommendation 19: Development of a national register of clinical trials Recommendation 19 The NHMRC should take a leadership role in working with State and Territory health authorities and other agencies to foster the development of a national register of clinical trials. Principal recommendations 20-21: NHMRC infrastructure for the development of clinical research Recommendation 20 The NHMRC should immediately establish a post for a full-time clinical academic to fulfil a catalytic role in promoting and coordinating clinical research initiatives. He or she should take responsibility for the NHMRC’s initiatives in the training, recruitment and retention of clinical researchers, the provision of adequate infrastructure support, and the development of partnerships with governments, health services, teaching hospitals, universities, professional societies and colleges, and foundations. Recommendation 21 The NHMRC should immediately increase resources available within its own Office for the support of clinical research. Unless sufficient resources are provided within the NHMRC, the recommendations of this report cannot be implemented. Core resources within the NHMRC are crucial to generate development of Australia’s capacity for clinical research.

NHMRC Clinical Research Working Group report 10 Specific recommendations that provide detail in relation to the principal recommendations given above are included at the end of Chapters 2, 3, 4 and 5 of this report. The specific recommendations in each chapter should be considered in conjunction with the principal recommendations.

NHMRC Clinical Research Working Group report 11 1 Introduction 1.1 Why the Working Group was established The NHMRC Research Committee established the Working Group on Clinical Research in response to (1) a perception that structural and organisational changes in the health system were adversely affecting the development of clinical research in Australia, and (2) criticism that its own practices and procedures were contributing to this deterioration. The Working Group was asked to investigate what could be done to: - produce more and better clinical research in Australia, - provide better support for research in clinical settings, - improve training and other opportunities for clinical researchers, and - promote public and professional recognition of the value of clinical research.

The difficulties confronting clinical research in Australia are analogous to problems that have been described in the UK and the USA (Goldbeck-Wood, 2000; Rosenberg, 1999; Campbell et al, 2001). Clinical research depends upon the commitment and support of clinical institutions. Yet despite the acknowledged contribution of clinical research to effective, evidence- based practice, and the need for clinical research to underpin improvements in the quality and safety of health services, clinical research is not necessarily recognised or valued as an essential component of clinical services. The pursuit of efficiency, and contemporary interpretations of accountability in the management of health services, have increased pressure on clinicians (including clinicians in teaching and research positions) to treat patients rather than do research that might improve care. As a consequence, traditional opportunities for health-service-funded clinical research in major clinical institutions have been eroded – and no substitute has emerged. The erosion of these opportunities is accompanied by an apparently-diminishing capacity of health-service institutions to recruit, train, provide mentorship for, and otherwise support new entrants into clinical research. It has also made the definition of a viable clinical-research training and career path very difficult, especially for individuals who plan to sustain a parallel clinical-service career. In particular, there are many indications that the budgetary pressures on health authorities are such that clinical researchers are no longer able to devote time or energy to serious research. Indeed, researchers report that the critical missing ingredient is the provision of protected time for the conduct of clinical research.

Alongside these structural difficulties, several organisational and funding issues relating to clinical research in Australia require resolution. Clinical researchers perceive that research-funding agencies, including the NHMRC, have inadequate mechanisms for the adjudication of clinical-research grant applications. The need to provide and sustain a public-sector infrastructure for clinical trials warrants urgent attention, including future support for one or more national clinical trials centres.

NHMRC Clinical Research Working Group report 12 Related to this is the need to specify mechanisms for public-sector funding of clinical trials and large-scale research involving the recruitment of patients. Of great importance for some forms of clinical research is the need for a consistent approach to the development and operation of disease registers and tissue banks. Ideally these should be linked to each other and to clinical data, and should not be encouraged to proliferate in isolation. 1.2 Terms of reference The Working Group’s terms of reference, as specified by the NHMRC Research Committee, are as follows: 1. To report to the Research Committee on the means whereby the NHMRC might work with other parties to: -strengthen and improve the quality of clinical research in Australia; -ensure that appropriate organisational structure and necessary infrastructure is provided for research in clinical settings; -improve research training opportunities for clinical researchers, to ensure a strong cohort for the next generation and, in doing so, examine different models of research training (eg Masters of Public Health at NCEPH and the Wellcome Program); and -consider mechanisms for the support of clinical trials and disease registers (including clinical trials centres, etc).

2. To consider how the importance of clinical research can be better promoted in Australian medical schools, and in the wider community. 3. To advise the NHMRC on how it could work effectively with other key bodies to improve clinical research, including the professional colleges, the universities, and other relevant organisations. Reference to be made to issues of capacity, workforce development, international links, industry opportunities, financial support, training and the relationship to professional bodies.

The Working Group was briefed to limit its review of and recommendations for the training and recruitment of clinical researchers to medical graduates, as the NHMRC was planning other mechanisms for reviewing training and recruitment of other clinicians involved in clinical research. 1.3 Definition of ‘clinical research’ After much debate, including consideration of US literature (Nathan, 1998; Schechter, 1998; Lee, 1999), members of the Working Group agreed on the following definitions.

NHMRC Clinical Research Working Group report 13 Research is a systematic process of inquiry, undertaken with the purpose of creating new knowledge that can be generalised to settings and subjects other than those studied. Clinical research is research involving human subjects in health and illness. It is done in response to a clinical research question, in order to inform clinical practice through the application of patho-physiological, population-based, behavioural or qualitative research methods. The research may be observational or interventional.

For the specific purposes of the Working Group, but not for wider application, members agreed that the following qualification should be added to the definition of ‘clinical research’: Clinical research includes research in which the investigator has experience of clinical practice, and in the course of which there is direct interaction between the investigator and the subjects (patients). It also includes other types of research which inform clinical decisions, such as meta-analysis and systematic reviews.

1.4 What the Working Group did Before the Working Group was convened, a reporter was engaged by the Office of the NHMRC to prepare background papers, carry out research, record the deliberations of the Working Group, and compile interim and final reports. The reporter worked closely with the Working Group’s Chair. The Working Group held three meetings in Sydney, on the following dates: 7 May, 4 July, and 24 August 2001. At the first meeting, members agreed to the following two major initiatives to consult the groups and individuals throughout Australia with an interest in clinical research.

(1) A letter from the Chair to the heads of some 70 educational bodies, professional societies and other agencies throughout Australia that have an interest in clinical research. In his letter, he asked for: - copies of relevant reports and/or relevant analyses and action plans; - views on priority issues that the Working Group should address, and recommendations for action to enhance the quality and vigour of clinical research in Australia; and - views on the development of an ongoing mechanism whereby all agencies concerned with the support of clinical research and training of clinical researchers could work together.

The letter was sent to Deans of Faculties of Medicine, Presidents of Medical Colleges and special societies, State and Territory Chief Medical Officers, and the heads of some other non-government organisations that support clinical research. (2) An e-mail ‘survey’ from the Office of the NHMRC, informing all the individuals on its list-server of the existence and intent of the Clinical Research Working

NHMRC Clinical Research Working Group report 14 Group, and inviting input. This ‘survey’ was intended as a consultative process and as a means of canvassing ideas, rather than as an attempt to obtain representative information regarding clinical research. Respondents were asked to: - enter any comments that they would like to make about clinical research; - give their views on areas that particularly related to the Working Group’s terms of reference, viz (a) infrastructure and funding for clinical research, (b) training of clinical researchers, (c) recruitment, retention and career development of clinical researchers, (d) support for clinical trials and other large-scale clinical studies, (e) collaborations and partnerships that enhance the capacity and effectiveness of clinician-researchers, and (f) the development of disease registers and tissue banks; and - provide some information about themselves to help in sorting the responses – whether or not they were involved in research, clinical research and clinical practice, their place in the career cycle (early, established, or senior), and their gender.

The ‘survey’ was distributed to some thousands of people, including those who had received NHMRC grants, reviewed grant applications, served on committees, etc. The responses have been collated and analysed (Appendix 3), and have contributed materially to this report. At the second meeting, the Working Group formed two Working Parties. • The first was a Working Party on Training, chaired by the Chair of the Working Group, and comprising mostly individuals co-opted because of their interest in clinical research and their ability to bring diverse perspectives to the debate. The objectives, deliberations and recommendations of the Working Party are given in Chapter 3, and the membership is listed in Appendix 1. • The second was a Working Party on Tissue Banks, comprising Working Group members, with one external adviser. The deliberations and recommendations of this Working Party are reported in Chapter 5, and the membership is also listed in Appendix 1.

NHMRC Clinical Research Working Group report 15 2 Current status of clinical research in Australia 2.1 Preamble As noted in section 1.1, the Working Group was asked to make recommendations on steps to produce more and better clinical research in Australia. In preparation for this, the Working Group attempted to gather information on the current status of clinical research in Australia from published reports, from websites, from NHMRC documents, and through the consultative processes described in section 1.4. Very little consolidated information on the current status of clinical research was available. This chapter provides a sketch of the current arrangements for clinical research, and gives a brief summary of available data on indicators of the quantity and quality of clinical research. Reports on information obtained in the consultative processes described in section 1.4 are given in Appendix 2 and Appendix 3. 2.2 Main sources of funding of clinical research The main sources of direct funding for clinical research in Australia are: - the NHMRC; - State and Territory health departments; - the private-sector health industry, particularly the pharmaceutical industry; - universities; - the clinical colleges; - foundations, such as the Clive and Vera Ramaciotti Foundations, the National Heart Foundation, and the Asthma Foundation; - other non-government organisations that represent particular health problems at national and/or State/Territory level, such as State-based anti-cancer councils, and the national groups with which they are affiliated.

Funding from these sources is used to support research projects and programs, infrastructure, and researchers in both training and in career positions, as follows. • State and Territory health departments (directly and through local health authorities or hospitals) employ staff specialists, many of whom have the opportunity to undertake research as part of their responsibilities; some of this research is clinical research. • State and Territory health departments support research-infrastructure funding programs, which are mostly directed towards particular research centres or institutes; some of these centres or institutes conduct clinical research. • A small proportion of the cost of running teaching hospitals throughout Australia goes towards the indirect costs of research; some of this is clinical research.

NHMRC Clinical Research Working Group report 16 • Universities employ clinical academics, often in conjunction with health authorities or hospitals; some of their research is clinical research. • The NHMRC, the clinical colleges, and non-government organisations fund research projects and programs, and also award scholarships and fellowships for researchers at various levels of seniority; some of these projects and programs are on clinical-research topics, and some of the scholars and fellows are clinical researchers.

• The pharmaceutical industry invests heavily in research and development, some of which is clinical, for example, evaluations of new drugs. In the preceding points, the emphasis falls repeatedly on the word ‘some’; some of the resources provided by the listed organisations goes towards clinical research, but it is practically impossible to say how much. Routinely-collected data on applications for research grants and grants awarded do not record whether research is ‘clinical’ or ‘non-clinical’. Indeed, there are no established criteria for the identification of ‘clinical research’. Rather, funded research is classified according to: - the type of grant program under which it is funded, e.g. project grant, program grant, new investigator grant, training award; - the institution to which grants are awarded, e.g. the University of New South Wales, the Baker Medical Research Institute; - the discipline, e.g. biostatistics, endocrinology, gastro-intestinal diseases and sciences, physiology, surgery; and - the field of research, e.g. clinical pharmacology and therapeutics, fetal development and medicine, oncology and carcinogenesis, rheumatology and arthritis (NHMRC, 2000). These taxonomies do not identify clinical research – for example, surgical research, or research in rheumatology and arthritis, can be clinical or non-clinical. Few, if any, Australian funding programs are exclusively directed towards clinical research, or contain exclusive clinical-research streams, however ‘clinical research’ is defined. Consequently, regular systems for monitoring health and medical research grants provide little information on the nature and extent of clinical research in Australia, or on clinical research expenditure. Analyses of trends in clinical research-grant applications and funding, such as those reported in the USA (Nathan, 1998; Goldberg, 1999), cannot be readily undertaken in Australia. Despite a lack of consolidated information, it is reasonable to assume that public- sector health services and the pharmaceutical industry are, directly or indirectly, the largest funders of clinical research; and that the NHMRC is the strongest single focus promoting the development of clinical research and clinical researchers. 2.3 Information on clinical research activity Because information cannot be obtained from these regular systems, the only way to find out about clinical research in Australia is to carry out special studies in which individual research proposals are examined prospectively or retrospectively, classified as ‘clinical’ or ‘non-clinical’, and described. This usually requires special data collection and analysis which, to our knowledge, have been attempted only a few times.

NHMRC Clinical Research Working Group report 17 An important example is a study commissioned in 1996 by a Clinical Research Working Party of the (then) Medical Research Committee of the NHMRC. This study was carried out by Dr M Faddy and Professor J Eccleston, of the University of Queensland, who reported on clinical and non-clinical research-grant applications to the NHMRC for the years 1989, 1991, 1993, and 1995. Over these four years, 23.5 per cent of the 4,577 research-grant applications received by the NHMRC were determined to have been for clinical research; the proportion varied from year to year without a clear trend. Consistently fewer clinical research applications were awarded grants than non-clinical applications – the average success rate for clinical-research applications was 23.3 per cent, compared with 30.6 percent for non-clinical research applications. The success rates for clinical-research applications ranged from 13.6 per cent in 1993 to 30.8 per cent in 1991; the corresponding range for non-clinical research was 26.9 percent (also in 1993) to 36.6 percent (also in 1991). (Medical Research Committee agenda papers for the meeting on 18 November 1996) The analyses of Faddy and Eccleston do not appear to parallel findings from the US National Institutes of Health (NIH). The success rates of physician-scientists applying for NIH project grants have been consistently similar to the success rates of non-physicians, but medical graduates have become a progressively smaller minority of those seeking and obtaining NIH project support. The number of first-time medically-qualified applicants for grants dropped markedly between 1994 and 1997, and the number of medically-qualified post-doctoral trainees supported by the NIH also dropped markedly from 1992. These findings suggest that progressively fewer young medical graduates were seeking careers as independent NIH-supported investigators (Goldberg, 1999).

Little information is available on participation in clinical research in Australia. Where information is collected on participation in research among clinician groups, it does not identify whether the research is clinical or non-clinical. For example, the Royal Australasian College of Physicians (RACP) publishes information on its Australian Fellows every two years, dividing Fellows into general consultants, specialist consultants, general paediatricians and specialist paediatricians. Their participation in research in 1999 was as follows.

Type of practice Number of Fellows Proportion participating in research* General consultant 498 32% Specialist consultant 2684 58% General paediatrician 403 29% Specialist paediatrician 451 75% Total 4036 54% *Type of research was not specified. Source: Dent O. The Royal Australasian College of Physicians clinical workforce in internal medicine and paediatrics in Australia, 1999. Fellowship Affairs, 2000 (March): 1-16. Participation in research did not appear to have varied much over the most recent four years surveyed (1993, 1995, 1997, and 1999).

NHMRC Clinical Research Working Group report 18 Recently-published studies have provided information on trends in general practice research. A five-fold increase was found in the amount of Australian general practice research published in the decade 1990-99, compared with the decade 1980-89. Approximately half of this research was described as ‘clinically pertinent to the front- line GP’, the remainder dealing with topics such as education and training and professional and organisational issues (Ward, Lopez and Kamien, 2000). Despite this increase, a considerable disparity exists between the research output of general practice and that of medicine, surgery and public health. Over the decade 1990-99, one general practice article was published per 1000 GPs in practice in Australia per year. Corresponding rates for medicine, surgery and public health were 105, 61 and 148 per 1000 respectively (Askew, Glasziou and Del Mar, 2001). 2.4 Information on support for clinical research 2.4.1 Support from the NHMRC Routinely-collected data on NHMRC research grants and fellowships do not specify support for clinical research (as distinct from other forms of research). However, in addition to project and program grants of various types, some NHMRC initiatives do focus mainly (if not exclusively) on clinical research. Funds allocated for these initiatives are indicative of the investment in clinical research, although they should not be taken as true estimates of clinical research funding. These initiatives include the following.

• Support for Centres of Clinical Excellence in Hospital-based Research (see section 4.6) • NHMRC Practitioner Fellowships. These are intended for experienced and productive clinical and public health researchers who wish to maintain both a research career and a role as a practitioner. Applicants must have a successful research track record. The scheme is intended particularly for researchers in early to mid career as a mechanism to facilitate the enhancement of future research capacity in clinical and public health. The value of Practitioner Fellowships is $100-120,000 per annum.

• Clinical Career Development Awards. These awards, to be introduced in 2002, are intended to enable investigators with at least three and no more than nine years’ post-doctoral (or equivalent) experience to develop themselves as independent, self-directed researchers. The awards are designed to expand the national research capacity and encourage translation of research into practice. They are available on a part- or full-time basis for five years (non-renewable), and have a value of $80-90,000 for full-time researchers.

• Australian Clinical Research Postdoctoral Fellowships and Neil Hamilton Fairley Fellowships. These Fellowships provide full-time training in clinical research. Applicants must hold a doctorate and should have no more than two years’ postdoctoral experience. Australian Clinical Research Postdoctoral Fellowships are awarded for a maximum of four years at an Australian institution. Neil

NHMRC Clinical Research Working Group report 19 Hamilton Fairley Fellowships are awarded for four years, of which the first two are spent overseas. • Australian Health Professional Research Training Fellowships and Australian Research Training Fellowships. These are available to provide part-time training in research, including (but not confined to) clinical research. The Professional Fellowships are particularly directed at individuals who do not wish to relinquish their professional career for a full-time research fellowship. Fellows are expected to work on their research for 50-70 percent of their time over three years. Australian Research Training Fellowships are intended for people who are returning to the workforce with an interest in pursuing a research career, and who do not have other research or clinical responsibilities. They are awarded on the basis of a 50 percent part-time rate for up to four years. In 2001, the NHMRC awarded: - seven new Practitioner Fellowships with a total value of $370,000 - four Neil Hamilton Fairley Fellowships with a total value of $321,000 - five Australian Clinical Research Fellowships (including two part- time) with a total value of $206,000.

2.4.2 Examples of other support from the Commonwealth, the Colleges, and non-governmentother organisations The following are examples of support for clinical research from the Commonwealth and organisations other than the NHMRC. The information given below was derived mainly from correspondence received in the course of the consultative process described in section 1.4. Commonwealth Department of Health and Aged Care The Commonwealth Department of Health and Aged Care has recently introduced the Primary Health Care Research Evaluation and Development (PHC-RED) Strategy, a $50 million program that aims to embed a research culture in Australian general practice and primary health care. It comprises five linked elements: establishment of primary health care research priorities; a scholarship and fellowship program; funding to develop research capacity in academic departments of general practice and rural health; a research grants program; and establishment of an institute for primary health care research. PHC-RED will provide an important mechanism for the support of clinical research in primary health care, and for the support of research collaborations and the development of research skills. Royal Australasian College of Surgeons The Royal Australasian College of Surgeons (RACS) has several initiatives that encompass support for clinical research. These include the following. • Research scholarships with a total value of $1.5 million each year. These scholarships are directed at ‘young researchers starting out in a research career

NHMRC Clinical Research Working Group report 20 and who will work in University Departments of Surgery in Australia and New Zealand.’ Information from the RACS suggests that clinical research figures strongly in the research undertaken by the scholars, who are mostly young surgeons. ‘To help manage this research effort, the College has a Board of Surgical Research [with a] part time Professor of Surgical Studies.’ (Correspondence from D Scott, Executive Director for Surgical Affairs, RACS, 14 September 2001) • The Surgeon Scientist Programme. This aims to improve recruitment to clinical academic surgery by promoting a combined PhD/FRACS qualification. A total of 12 Surgeon Scientists were funded in 2001. (Correspondence from D Scott, Executive Director for Surgical Affairs, RACS, 14 September 2001) • The Australian Safety and Efficacy Register of New Interventional Procedures – Surgical (ASERNIP-S). ASERNIP-S carries out systematic literature reviews and collects and analyse data on selected surgical procedures. It is located in Adelaide, and is funded under contract from the Commonwealth Department of Health and Aged Care. (ASERNIP-S 2000 Annual Report) Royal Australasian College of Physicians and the Australian and New Zealand Society of Nephrology A good example of clinical-research support is the use of a bequest to the Royal Australasian College of Physicians (RACP) from the estate of Don and Lorraine Jacquot to establish the Jacquot Collaborative Clinical Research Initiative Grant scheme. The scheme is intended to fund clinical research projects in renal disease, with preference for multi-centre randomised clinical trials; and ‘to fund the training of an advanced trainee or young nephrologist as a fellow in clinical epidemiology and clinical trial design/practice’. Up to $250,000 will be committed to a project each year for three years, starting in 2002. The scheme is jointly managed by the RACP and the Australian and New Zealand Society of Nephrology (ANZSN). (Correspondence from B Murphy, President, ANZSN, 4 July 2001) Anti-Cancer Council of Victoria The Anti-Cancer Council of Victoria (ACCV) supports several initiatives in clinical research associated with cancer. These include the following. (Correspondence from R Burton, Director, ACCV, 27 July 2001) • Infrastructure and funding for clinical trials. The ACCV has a long-term commitment to clinical research through its Centre for Clinical Research in Cancer and the activities of the Victorian Cooperative Oncology Group. Support for infrastructure and trials is provided through a Clinical Trials Management Scheme and Clinical Trials Office. The aim of the Scheme is to assist clinicians to participate in clinical trials. The Clinical Trials Office provides advice in the development of protocol design and coordination of the conduct of clinical trials initiated by the Victorian Cooperative Oncology Group. The ACCV budget for clinical trials research in 2001 amounted to $595,000

NHMRC Clinical Research Working Group report 21 • Population-based surveys of cancer clinical management. The ACCV funds studies of the management of particular cancers. The annual budget for these studies is $55,000. • Registers of in-situ and small invasive breast cancer, radical prostatectomy, and hepatocellular carcinoma. These three cohort registers of clinical management and follow-up were established within the Victorian Cancer Registry, and are funded primarily through the ACCV budget.

2.5 Specific recommendations No consolidated information is available on the quantity and quality of clinical research in Australia. Our knowledge of the current status of clinical research is a patchwork with many pieces missing, upheld by many anecdotes in which clinicians, researchers, and research-policy makers consistently draw attention to deficiencies in the support of clinical research. The following recommendations are intended to enable the development of an information base on clinical research in Australia. 2.5.1 Development of criteria for classification of ‘clinical research’ and monitoring of clinical research Recommendation 2A The NHMRC should formulate criteria for classifying research-grant applications as ‘clinical’ or ‘non-clinical’, and should develop mechanisms for monitoring the extent and quality of clinical research and the capacity for clinical research in Australia. Other agencies that fund clinical research in Australia should be encouraged to use the same criteria.

Recommendation 2B The NHMRC should commission a study of the current extent and quality of clinical research funded by major research granting agencies in Australia, including the NHMRC itself. This could be a new study, or it could build on existing data collections.

NHMRC Clinical Research Working Group report 22 3 Clinical research training 3.1 Scope of clinical research training Training in clinical research comprises vocational clinical training in a clinical discipline, and training in research methods. Broadly, training in research methods has three purposes: • First, initial formal research training, which provides individuals entering clinical- research careers, as well as clinicians interested in research, with knowledge, skills and experience in research methods. This training can cover both the specific methods used in particular fields of research, and the general concepts that apply more broadly across many fields of health and medical research. • Second, continuing education, which enables established clinical researchers to maintain their knowledge, skills and experience in research methods, and to acquire new skills and knowledge.

• Third, intellectual renewal. The strength, quality and integrity of health services depends upon their capacity for renewal through education and training, linked with a capacity to seek, absorb and apply new knowledge through research. The Working Group, and its Working Party on Training, concentrated on the first of these functions (initial formal training in clinical research), and on the links between clinical research and vocational clinical training for medical graduates. Discussion in the Working Group and the Working Party was confined to the training of clinicians in clinical research, rather than the training of individuals entering clinical research from non-clinical backgrounds, or the training of clinicians entering non-clinical areas of health and medical research.

The Working Group and the Working Party investigated and discussed - the training expectations and needs of clinicians entering clinical research, - training program structures and curricula, and - funding for clinical-research training. 3.2 Training expectations and needs of clinicians entering clinical research Clinicians entering clinical research, and clinician-researchers who reflect on their own developmental process, express a need for: - structured rather than ad-hoc research training; - mentorship, with mentors who encourage both their clinical training and their research training;

NHMRC Clinical Research Working Group report 23 - intercalation of research training with clinical training, so that clinical skills can be maintained while research skills are being acquired, and vice versa; - clinical training programs that facilitate, rather than militate against, research training (for example, by requiring frequent rotations among different hospitals); - protection of remuneration, to avoid very large fluctuations in income between clinical and research posts; - intellectual and physical environments that value clinical research; - training program structures that minimise the total duration of clinical and research training, and enable participants to establish families and participate in family life; and - a need for a career structure in clinical practice that offers significant opportunities for research.

The recommended action points listed at the end of this chapter propose steps than could be taken to meet these needs and expectations. In formulating the recommended action points, the Working Party identified an important distinction between formal research training for a clinician who intends to pursue clinical research as a major component of his or her career, and the clinical trainee who is required to do some research within a clinical-training program but does not intend to pursue a research-oriented career. Individuals with these different interests have different needs for training and different motivations, and different approaches to training are required to provide for them.

Moreover, the degree of emphasis on research in training programs varies among different fields. For example, vocational training for general practice carries little or no expectation of research training. Because general-practice trainees spend most of their time in community practice (rather than in institutions where research is traditionally done), general-practice trainees are often deprived of opportunities to obtain research training and undertake research projects. In contrast, trainees in internal medicine and surgery often have good opportunities to obtain research training, and often work in teaching hospitals where they can be exposed to clinical research activity. Several specialist clinical colleges actively support research training, usually for any type of research of disciplinary relevance (not just clinical research). For instance, the Royal Australasian College of Surgeons (RACS) Surgical Scientists program allows trainees to undertake advanced surgical training and to complete a PhD, with one overlapping year, and the RACS Research Foundation awards three-year scholarships to encourage PhD studies. 3.3 Training program structures and curricula 3.3.1 The current situation Clinicians who seek training in research in Australia can pursue several options. For example:

NHMRC Clinical Research Working Group report 24 - they can apply for a research scholarship or fellowship from a wide variety of organisations (including the NHMRC, the clinical colleges, and non-government organisations such as the National Heart Foundation and State-based cancer councils), and undertake a research project under supervision; - they can seek support from a university and, again, undertake a research project under supervision; - they can seek local support from a health-service institution such as a teaching hospital, a regional health authority, or a Division of General Practice, and again, undertake a research project, with or without supervision; - they can undertake coursework that covers research methods (such as a clinical epidemiology program), funded either from their own resources or from a scholarship; or - they can embark on research within their own practice, learning as they go and possible obtaining ad hoc advice from colleagues. These options may or may not be linked to a higher degree program, or form an accredited component of a post-graduate vocational qualification such as Fellowship of the Royal Australasian College of Physicians.

Whichever clinical-research training route is followed, several organisations are likely to be involved in the training of an individual. These typically include: (1) a hospital or other clinical-service institution, which provides the setting for the research, and may employ the individual undergoing training; (2) a university, which is usually linked with (1), and may provide academic training and supervision; (3) a clinical college, which provides an accredited underpinning of the clinical side of the clinician-researcher’s life, and may support the research-training process; (4) an agency which funds the research project; and (5) an agency which supports the individual undergoing training. There may be overlap between (1), (2) and (3) on the one hand, and (4) and/or (5) on the other.

At present there is no coordination among these organisations, and it is up to the individual who undergoes training to negotiate his or her relationship with all of them. Often he or she must also manage the connections among the organisations (and individuals within them) that are needed to ensure that his or her funding, research- training, clinical-training, clinical-service, and other life requirements are met. This can be a complex process, and underlines the observation that training and career structures are lacking.

3.3.2 Coursework in research-training programs Clinical-research training in Australia is usually experiential: the clinician embarks on a supervised research project without much (if any) training in research methods. He or she learns about research while doing it, or may undertake courses on an ad-hoc

NHMRC Clinical Research Working Group report 25 basis to acquire expertise as needed, for example in statistical methods. Thus even where research training is undertaken within a university-based higher-degree program, it is structured as an apprenticeship. Concentration on experiential training tends to give researchers a deep but relatively narrow understanding of research methods, confined mainly to the research paradigm in which they work. It has been suggested that this type of training does not give researchers the adaptability that equips them to participate in multi-disciplinary research. Conversely, it has also been suggested that the inclusion of research- methods coursework in postgraduate research-degree programs improves the effectiveness of researchers in multi-disciplinary collaborative studies. The Working Party therefore assessed the value of structured training in research methods, including coursework. Three levels of training were identified: 1) Certificate-level training in generic research skills, giving clinicians a basic understanding of contemporary research methods and the ability to find and use research-based knowledge in their practice. Core skills are listed in section 3.3.3. Some Australian teaching hospitals are known to provide regular training sessions in these core skills.

2) Master’s-degree programs that provide rigorous training in research methods. Different options exist for getting such training, including full-time and part-time coursework (with evening classes, clinicians can maintain daytime clinical jobs). 3) Doctoral programs that include coursework in research methods. A doctoral degree (usually a PhD) is regarded as the core requirement for a research career alongside a clinical career. Unlike many North American doctoral programs, Australian doctoral programs – particularly PhDs – rarely include coursework. The Working Group and the Working Party on Training strongly endorsed the value of including rigorous coursework-based training in research methods in doctoral research degrees. It was proposed that the NHMRC could stimulate a few Australian universities to develop model doctoral programs that included coursework in research methods. Academic programs would, of course, have to be linked with clinical-research settings in which the training could be applied. The development of course-based modules of research training was also favoured. Course modules could be available across institutions, and potentially could be taken by trainee clinical researchers in different disciplines. They could be incorporated in PhD and other doctoral programs, such as the MD. The disadvantage is the high cost of developing modules, which could be prohibitive for individual institutions. However, sharing modules among institutions could be a feasible solution, enabling each major centre to run courses in a range of fields without bearing the full cost of curriculum development. The possibility of clinical colleges sharing the provision or support of research-methods courses that are common to many clinical-research disciplines warrants consideration.

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NHMRC Clinical Research Working Group report 26 3.3.3 Generic research skills for all clinicians Members of the Working Party on Training agreed that basic research skills should be a part of vocational training in all clinical fields. These skills would enable clinicians to undertake evidence-based practice and to participate in clinical research as part of their clinical career. They represented minimal requirements and would not be adequate for those who plan to pursue a fully research-oriented career. The Working Party identified the following as generic research skills that all clinical trainees should acquire: • Formulating literature review questions • Literature searching • Critical appraisal of research reports • Interpreting basic statistics • Management of a database and basic data presentation • Scientific writing and scientific presentations • Formulating a research question • Study design The Working Party concluded that training to develop core skills for clinical research should be provided at three stages: • In undergraduate and graduate medical programs • During the first 2-3 postgraduate years • In advanced vocational training programs. Many Australian medical schools already provide generic research training in undergraduate or graduate medical courses. Medical schools that do not provide such training should be encouraged to develop it and to ensure basic minimal standards are achieved.

Research training can be intercalated with undergraduate or graduate medical programs (leading to a combined degree), or with postgraduate vocational training, such as that for Fellowship of the clinical colleges.. Both have advantages and disadvantages, the former anchoring the research training earlier into the individual’s career development, and the latter providing a better intellectual basis for linking clinical experience with the development of research skills. Working Party members drew attention to the need to connect formal clinical- research training programs with mentorship. Desirably this would give the prospective clinical researcher access to support from established clinical researchers, who could provide advice on how to structure an appropriate clinical-research training program and subsequent career opportunities.

NHMRC Clinical Research Working Group report 27 3.4 Funding of clinical-research training Funding of clinical-research training has three components: • remuneration for the individual who undertakes research training; • infrastructure funding to enable research training to occur, including the cost of mentorship; and • funding of research projects undertaken in the course of training. As regards remuneration for individuals who undertake research training, many scholarships and fellowships are available from a wide variety of sources. Almost all of these scholarships and fellowships provide a rather low level of remuneration. The pay is much less than a clinician would receive, even at the earliest stage of post- graduate clinical training. Given the age and life-stage of clinicians who seek to enter research, scholarship- or fellowship-based remuneration is usually insufficient. It is therefore common for researchers who accept scholarships and fellowships to take on part-time clinical jobs alongside their research. While this enables them to maintain their clinical currency, it is often a major compromise.

Dedicated infrastructure funding for research training and dedicated funding for mentors are rarely available in Australia. Infrastructure funding related to training needs is usually drawn from other institutional research infrastructure. Recent programs introduced by the US National Institutes of Health provide that, for every individual awarded a particular type of NIH training fellowship, the NIH provides a significant proportion of the salary of a mentor in addition to the remuneration of the trainee (Nathan, 1998).

Research-project funding for projects undertaken during training is usually derived from the same sources as funding for other research projects. Success in applying for research grants invariably depends upon the trainee submitting an application with his or her mentor or supervisor. The application process can be an important training experience, but it can introduce long delays, including long periods of uncertainty as to the viability of research-training plans. Many existing institutions, structures and processes represent potential resources that could be tapped to support clinical-research training, either with funding or in kind. For example, nationally-funded clinical trials centres (described in section 4.5) and Centres of Clinical Excellence in Hospital-based Research (section 4.6) could be required to provide clinical-research training and mentorship as a condition of their funding. The same could apply to institutions and clinical researchers selected to participate in the proposed Clinical Practice Research and Development Scheme (section 4.2). Existing national- and state-based organisations such as the National Institute of Clinical Studies (NICS) and the NSW Institute of Clinical Excellence (ICE) could be encouraged to ensure that clinical-research entities which they fund provide training and mentorship.

NHMRC Clinical Research Working Group report 28 3.5 Specific recommendations In formulating recommendations, the Working Group and its Working Party on Training focused on the following issues. • The need for a substantial, sustained national investment in clinical-research training. • The need for leadership in coordinating the numerous agencies directly or indirectly involved in clinical-research training. • The need to build existing institutions, structures and processes for both the support and the delivery of clinical-research training.

• The importance of accommodating the varying requirements and expectations of clinical-research trainees. Arising from these issues, the following specific recommendations were proposed 3.5.1 Recognition of the importance of clinical-research training Recommendation 3A The NHMRC and other relevant agencies should make a substantial and sustained investment in clinical-research training, recognising that clinical research is essential for the strength, quality and integrity of Australian health services. It should be recognised that the development of clinical research, and the entry of talented graduates into careers with a clinical-research orientation, depends ultimately upon strong support from universities, clinical colleges, and health authorities throughout Australia.

3.5.2 Development, coordination and support of clinical-research training Recommendation 3B The NHMRC should lead, sponsor and broker efforts to develop and coordinate training in clinical research among the numerous organisations involved, including hospitals and other clinical institutions, regional health services, government departments, universities, the clinical colleges, and agencies which fund research and provide scholarships and fellowships, such as the NHMRC. These efforts should aim to provide structured opportunities and a clearer path for career development in clinical research. They should include support for the development of a career structure that combines clinical research and clinical practice, and is available as a career option for current clinical trainees who have a strong interest in and aptitude for research.

Recommendation 3C New initiatives in clinical-research training and coordination efforts should build on existing mechanisms that address pre-vocational and vocational medical education and training. In leading the development of clinical-research training, the NHMRC

NHMRC Clinical Research Working Group report 29 should work with established organisations that have responsibility for medical education and training. Recommendation 3D Following from Recommendation 3B and 3C, and as described in section 4.7, the NHMRC should fund a full-time position for a senior clinical academic with a capacity for high-level liaison and program development (referred to below as the ‘clinical research coordinator’). This individual should fulfil a catalytic role in promoting and coordinating clinical-research training initiatives among regional health services and hospitals, Commonwealth and State health departments, the clinical colleges, universities, other groups involved in postgraduate and continuing medical education, and research-funding agencies.

Recommendation 3E At any early stage, the NHMRC clinical research coordinator (see Recommendation 3D) should brief key groups such as the Presidents of Medical Colleges, the Council of Deans of Australian Medical Schools, and State-based groups such as the NSW Medical Education and Training Council about the need for promotion and coordination of clinical-research training, and discuss opportunities and mechanisms for joint action between these groups and the NHMRC. This is a pre-requisite for the national workshop on clinical research (see Recommendation 3F). Recommendation 3F The NHMRC should sponsor a national workshop of representatives of the numerous agencies that have an interest in clinical research, either as funders, or as providers of vocational training, or as employers of clinicians and clinician researchers. This workshop should take place only after appropriate consultation with these agencies has taken place and their endorsement of it has been obtained. The workshop should deal with the development and coordination of clinical-research training. It should seek to engage agencies that might support clinical-research training, and should provide a forum for discussion of opportunities and mechanisms for joint action between these groups and the NHMRC. Prior to the workshop, the NHMRC clinical research coordinator should brief key participating groups and seek their ‘buy-in’ into the action that will follow the workshop (see Recommendation 3E).

Recommendation 3G The NHMRC Executive and the Chairs and Chief Executives of the NICS and state- based organisations such as the NSW ICE should explore opportunities for joint support of clinical-research training. They should aim to provide a capacity for clinical research that can fulfil governments’ commitments to improving the safety, quality and effectiveness of health services, including the development and implementation of evidence-based practice. Recommendation 3H Agencies which support clinical-research training, such as the NHMRC, should be encouraged to concentrate their resources on providing stable funding for institutions that run training programs, not just on the funding of individuals who undertake training programs.

NHMRC Clinical Research Working Group report 30 Recommendation 3I In its current analysis of options for the development of the national health and medical research capacity, the NHMRC should ensure that the support of clinical- research training is substantially enhanced and built into established research-funding processes. For example, the NHMRC could impose a requirement to provide for research training in larger grants that have a clinical-research component. Recommendation 3J A tangible commitment to provision of clinical-research training should be an essential condition for the NHMRC’s award of large grants for Centres of Clinical Excellence, clinical trials centres, and other institutions or networks involved in clinical research.

3.5.3 Training program structures Recommendation 3K Clinical-research training programs should have the flexibility to accommodate the different needs, backgrounds, and professional and domestic circumstances of potential trainees, and the nature of the research which they intend to pursue. Broadly, trainees should have access to: - specialist research training for full-scale career development in clinical research, as well as more limited, generic research training for clinicians who have an interest in research but not as a major part of their careers; - part-time and full-time posts; - research-only posts; and - posts that variously combine research training with clinical training, either at the same time, or in alternating blocks, so that both clinical and research skills can be acquired and maintained. Modular training programs (see Recommendation 3N) could provide the flexibility needed by many trainees. As one of the flexible options, the clinical colleges should provide for vocational clinical trainees to devote one fully-accredited year of their overall training program to clinical-research training, with appropriate mentorship from senior clinicians who have a research track record. For this option, trainees could continue with some clinical practice alongside the research, with at least 50% of their time protected for research training.

Recommendation 3L The NHMRC, through the clinical research coordinator (see Recommendation 3D), should examine the feasibility and potential benefits of incorporating coursework in Australian research-degree programs, including doctoral programs, with particular reference to clinical-research degrees. North American doctoral research-degree programs, which commonly include coursework, should be reviewed. The use of coursework in population-health-based research-degree programs at master’s and doctoral levels conducted by several universities throughout Australia should also be assessed.

NHMRC Clinical Research Working Group report 31 Recommendation 3M Subject to a positive outcome from the review described in Recommendation 3L, the NHMRC should provide incentives to a few Australian universities to develop model doctoral programs that might include coursework in research methods. These programs should be developed in academic settings which have strong links with clinical services. They should be developed to become widely recognisable as a prestigious qualification that assures rigorous research training. Recommendation 3N The NHMRC should provide incentives to networks of Australian institutions (including universities and clinical colleges) to develop coursework-based modules of research training that could be available across institutions, offered to trainee clinical researchers in different disciplines, and possibly incorporated in doctoral and other programs. These networks should defray the high cost by sharing the developmental effort among participating institutions.

3.5.4 Meeting the training expectations and needs of clinicians entering clinical research Recommendation 3O In addition to flexibility of training posts (see 3.4.1), clinical-research training programs should meet the basic needs of participants. These include: - intellectual and physical environments in which clinical research and research training are valued and supported; - mentorship (see Recommendation 3P); - appropriate clinical-service arrangements that do not impede research (for example, by requiring frequent rotations among different hospitals); - adequate remuneration, with research remuneration being equivalent to clinical-service remuneration.

Recommendation 3P Clinical-research training programs should emphasise the value of mentorship. Organisations which support clinical-research training should ensure that trainees have access to clinical and research mentors who appreciate the importance of, and promote, clinical research and research training. Mentors should serve as role models; both men and women with a variety of different commitments and interests should be encouraged and promoted as mentors. The availability of appropriate mentorship should be a criterion in the award of grants under the proposed Clinical Practice Research and Development scheme (see section 4.2) and in the Centres of Clinical Excellence program (see section 4.6), and a condition of funding of clinical trials centres. The NHMRC, through the clinical research coordinator, should examine the practice of the US National Institutes of Health (NIH), which established a special program whereby for individuals awarded an NIH clinical research training fellowship, the NIH provides a significant proportion of the salary of a mentor in addition to the remuneration of the trainee.

NHMRC Clinical Research Working Group report 32 Recommendation 3Q Given the length of specialist training programs, it should be recognised that many of those with an interest in clinical-research training will need to blend their professional aspirations with child-bearing and child-rearing. Clinical-research training programs should be able to accommodate these requirements without placing undue stress on trainees. In general, clinical/ clinical-research training programs should be designed to limit the total duration of training.

3.5.5 Training program curricula Recommendation 3R All clinical trainees should acquire some core research skills as part of their training, s that they can undertake evidence-based practice and pursue some clinical research as part of their clinical career. These skills are minimal requirements and would not be adequate for those who plan to pursue a research-oriented career. Recommended core skills are as follows: - formulating literature review questions; - literature searching; - critical appraisal of published research; - interpretation of basic statistics; - management of a simple database and presentation of basic data; - scientific writing and scientific presentations; - formulating a research question; and - principles of research design. Recommendation 3S Training to acquire the core research skills listed in Recommendation 3R should be available at each of three critical stages: - in undergraduate or graduate medical programs; - in the first three years following graduation; or - in advanced clinical-training programs. All Australian medical schools should provide training in core research skills, using accessible and flexible modes of instruction. Medical schools and other institutions which provide clinical-research training should also give practical, project-based assistance and advice to trainees on the initiation of research, literature searching skills, scientific writing, and statistical methods.

Recommendation 3T Clinical-research training programs should accredit Master of Public Health, Master of Clinical Epidemiology and analogous degree programs for individuals who wish to develop expertise in clinical epidemiology and other population-health-based methods that are applied in clinical research. These degree programs should be recognised as contributing towards fellowships of clinical colleges.

NHMRC Clinical Research Working Group report 33 4 Maintaining clinical research capacity 4.1 Preamble Three mutually-dependent ingredients are essential to sustain clinical research: - time for individuals with established expertise to do research, alongside clinical responsibilities; - skills - maintaining skills in, and keeping up to date with, research methods and techniques; - resources, in the form of both infrastructure and funding for projects. A positive time – skills – resources cycle enables clinical research to flourish. Clinicians need time to do research, develop and maintain research skills, apply for competitive funding, and secure other resources for research. They must have the skills needed to obtain competitive funding, and to carry out research. They must secure resources, not only to have the means and facilities for research activity, but also to be able to dedicate non-clinical time for research.

However, it appears that, in many settings in Australia, the time – skills – resources cycle is operating in a negative mode, draining clinicians of the time, energy, and capacity to participate in research, and diverting potential clinical-research resources either to other aspects of health-system activity or to other forms of research. As noted in Chapter 1 of this report (section 1.1), the pursuit of efficiency, and contemporary interpretations of accountability in the management of health services, place great demands on clinicians (including clinicians in teaching and research positions) to treat patients rather than do research. Budgetary pressures in the public sector, and competitive pressures in the private sector, militate against the provision of resources for clinical research from mainstream health-service budgets. In this chapter we propose some steps to correct this destructive cycle. These steps comprise: • the establishment of a Clinical Practice Research and Development Scheme (section 4.2); • improvements to NHMRC clinical-research assessment processes (section 4.3); • development of mechanisms for the support of clinical trials and large-scale patient recruitment research (section 4.4); • expansion of support for clinical trials centres and provision of infrastructure support for clinical trials networks and other clinical research networks (section 4.5); • enhancement of the program supporting Centres of Clinical Excellence in Hospital-based Research (section 4.6); and

NHMRC Clinical Research Working Group report 34 • provision of sufficient capacity and infrastructure within the Office of the NHMRC to sustain the NHMRC’s leadership role in clinical research (section 4.7). If clinical practice is to be based on the best available evidence, relevant research is needed to generate quality evidence. If the use of evidence is a criterion for the evaluation of health services, it follows that performance criteria for accreditation of hospitals and other health facilities should include measures relevant to clinical research. Examples of such measures are the certain proportion of patients entering clinical trials, a certain proportion of trainees completing higher degrees, and a track record of clinical-research publications and clinical trials approved. 4.2 Clinical Practice Research & Development Scheme We propose that a national clinical-research investment scheme targeted at fully- fledged clinicians in research should be established. This could be known as the ‘Clinical Practice Research and Development’ (CPR&D) Scheme. 4.2.1 Objective The proposed overall objective of the CPR&D Scheme is to provide a sustainable capacity for clinical research in major clinical-teaching facilities (both hospital- and community-based) throughout Australia. The scheme is intended to: - promote recognition of the value of clinical research; - provide a structure for investment in clinical research by government and non-government funding agencies; - support clinical research within clinical institutions; - support clinician researchers; - enhance capacity for training and mentorship in clinical research; - improve the quality of clinical research in Australia; and - provide a highly-visible potential career structure for clinician researchers.

4.2.2 How the CPR&D Scheme would work Under the CPR&D Scheme, which would be implemented progressively over 10 years, up to 600 clinician-researcher posts throughout Australia would be part-funded to an average extent of $50,000 per post per annum (indexed), i.e. an average of approximately 30 per cent of the total cost of the remuneration package of a staff specialist. Individuals appointed to the posts would have a suitable title, such as ‘Senior Research Clinician’. In the first year, 60 posts would be established at a total cost of $3 million – an average of one or two posts in each significant clinical- teaching facility in medicine in Australia. While most of these organisations would be teaching hospitals, a significant proportion would be community based, fostering clinical-research development in general practice, community-based mental health practice, child health, and other population-based specialties. In the second year, a

NHMRC Clinical Research Working Group report 35 further 60 posts would be established, making 120 posts in all, at a total cost of $6 million. In the third year, a further 60 posts again would be established, making 180 posts, and so on, until the tenth year, by which time all 600 posts would be operational, costing $30,000,000 per annum nationally. The individual holding each post would be expected to spend a flexible proportion (say 20-50 per cent) of his or her time: - developing and maintaining a clinical-research program, - seeking external project funding, and - serving as a mentor to more junior clinicians interested in clinical research.

The sum awarded for each post would be flexible, and would parallel the proportion of time that the individual holding the post could commit to clinical research. The individual could be employed full-time or part-time. The funds for each post could either go towards the remuneration of the clinician-researcher, or could be used to ‘backfill’ clinical services in the institution, thereby freeing the clinician-researcher to commit time and energy to research. The duration of each post would be five years, and could be renewable. Tenure over the five-year period would be subject to regular performance review.

Clinical institutions eligible to participate in the CPR&D Scheme would have to demonstrate that they: - have or can provide infrastructure to support clinical research; - can form collaborative networks with other research institutions that have an interest in clinical research; - can provide training and mentorship in clinical research; and - have affiliations with a tertiary education institution. As a guide, participating institutions would be expected to provide infrastructure support, including staff, facilities and services, at a level that matches the funds awarded under the scheme.

Each funded post would be the subject of a specific application which would be peer reviewed. Assessment criteria for the award of funds would include: - the track record, qualifications, skills and potential of the applicant; - the contribution of the institution to the post; - the capacity of the institution to provide mentorship for clinical research; - the potential for the funded post to be involved in the development of networks and collaborations; and - accountability arrangements relating to the use of the funds awarded. The CPR&D Scheme should be distinguished from the NHMRC Practitioner Fellowship program, introduced in 2001. This program provides up to 50 percent of the salary of a researcher with post-doctoral experience, on the pre-condition that the recipient has also been awarded a research-project grant.

Implementation of the Scheme would depend upon the support of Commonwealth, State and Territory health ministers and health departments, as well as the NHMRC Executive.

NHMRC Clinical Research Working Group report 36 4.2.3 Funding The CPR&D Scheme should be funded jointly by Commonwealth and State governments, the NHMRC, and the clinical colleges, with a large proportion of the costs being met by the governments of the nine jurisdictions. It may also be possible to attract sponsorship from non-government organisations such as the National Heart Foundation, the Asthma Foundation, the Australian Cancer Society, and State-based cancer councils; the corporate sector; medical schools; and societies such as the Australian Medical Association. The NHMRC could be the broker of the scheme. It could not be the primary funder, but it could offer a contribution of funds. Hypothetically, contributions might be as follows: Source Proportion contributed Contribution in 1st year Contribution in 5th year Contribution in 10th year Common- wealth 30% $ 900,000 $ 4,500,000 $ 9,000,000 NHMRC 10% $ 300,000 $ 1,500,000 $ 3,000,000 States/ Territories 50% $1,500,000 $ 7,500,000 $15,000,000 Other* 10% $ 300,000 $ 1,500,000 $ 3,000,000 *’Other’ includes colleges, universities, foundations, non-government organisations, and the private sector.

Each State’s or Territory’s contribution would be used to support posts within the jurisdiction from which the contribution emanated. States’ and Territories’ contributions would be in proportion to their populations. Thus NSW would contribute approximately one-third of the States’ and Territories’ total contributions, and one-third of the posts would be located in NSW; Victoria would contribute approximately one-quarter, and one-quarter of the posts would be in Victoria; Queensland approximately one-fifth; and so on. Contributions from clinical colleges could also be earmarked for support of clinical research in the respective clinical disciplines.

The funding for each post would be sustained for one five-year cycle. At the end of the first cycle, the institution could apply for the post to be funded for a further cycle. The funds should be new funds, and should not be derived from reallocation of existing clinical research resources. 4.2.4 Advantages and disadvantages The CPR&D Scheme has several advantages. • First, it potentially restores resources for clinical research, which are said to be disappearing from mainstream health-service budgets.

NHMRC Clinical Research Working Group report 37 • Second, it helps to provide career opportunities and consistent stimulus and support for clinical research, through mechanisms that could be set up to be reasonably well buffered against the effects of current and future health-system reforms. • Third, it modifies the demand for clinical-research funding from local health- service budgets, which are usually under great pressure from competing local service-delivery demands. • Fourth, it establishes a shared scheme which can have both a national identity and an identity that relates to each funder.

• Fifth, because multiple funders would contribute, the burden on individual funders is reduced. The major disadvantage of the Scheme is the difficulty of implementing it. • A long-term commitment is required from at least 15 potential funders, ranging from the Commonwealth Government to clinical colleges. • Agencies which support the Scheme are likely to do so by shifting funds from other worthwhile research-support initiatives, rather than finding ‘new’ funds. • The Scheme also requires a significant effort of coordination to ensure that the funded positions contribute to the overall objectives of the Scheme, while allowing for considerable flexibility in the use of the funds in the participating institutions.

• Designing a widely-supported mechanism and process for the disbursement of the funds to support the individual posts is a significant challenge. There would be a requirement for this mechanism to ensure that the funds remain in the State or Territory in which they originate. • The existence of the Scheme should not lead to a compensatory reduction in funds from other sources, and institutions which do not receive funds from the scheme should not be discouraged from a commitment to clinical research. Moreover, there is a need to ensure that the Scheme does not lead simply to a reinforcement of current research-support arrangements, without promoting new entrants. 4.2.5 Evaluation Progressive evaluation of the CPR&D Scheme would be essential. The evaluation should assess the processes of disbursement of the funds to individual posts, and the use of the funds. It should also determine whether or not the Scheme is enhancing clinical research in ways that can ultimately improve clinical practice.

NHMRC Clinical Research Working Group report 38 4.2.6 Communication Mechanisms of communication should be established among the institutions involved in the CPR&D Scheme. These could include an annual or bi-annual national clinical- research conference at which clinician-researchers supported by the CPR&D Scheme would have an opportunity to present their work and build collaborations. 4.2.7 Linkages The CPR&D Scheme should be linked with other national initiatives designed to promote and support clinical research. These include the support of clinical trials centres, infrastructure support for clinical research networks, clinical trials and other large-scale studies, and Centres of Clinical Excellence.

4.3 NHMRC clinical-research assessment processes In the course of its consultations, the Working Group received numerous complaints from clinical researchers that arrangements within the NHMRC for assessing research-grant applications militated against the success of clinical-research applications. Because other research-funding agencies modelled their assessment procedures on those of the NHMRC, clinical researchers reported that their opportunities for obtaining project funding were almost non-existent. The problem was greatly compounded by the lack of health-service funds for clinical research, noted in section 4.1 above.

The Working Group also received anecdotal comments from members of NHMRC Grants Review Panels (GRPs) or discipline panels, who affirmed clinical researchers’ impression that clinical-research applications tended to be viewed unfavourably. Two reasons were given to explain this. First, clinical-research applications were often found to be of poor quality. Second, GRPs usually comprised biomedical researchers and public-health researchers, but few (if any) GRPs contained clinical researchers. Consequently advocacy for clinical research within GRPs was lacking, and it was therefore difficult for most GRPs to assess the value of clinical-research proposals, or to determine the adequacy of the proposed research design and methods. These comments, from both clinical researchers and GRP members, suggested a need for GRPs to have a capacity for a more comprehensive assessment of clinical research than exists at present. Accordingly, the Working Group recommends that a number of GRPs (say four or five GRPs, between them covering a broad range of fields) should have an interest and expertise in clinical research. These panels should have four or five clinician-researcher members who could assess and champion clinical- research applications appropriately. Clinical-research applications could then be channelled to these GRPs. These GRPs should be in addition to the GRP proposed for clinical trials and large-scale patient recruitment research, proposed below (see section 4.4). Appropriate clinician membership should be extended to other discipline panels where clinical research or research topics of clinical relevance are considered.

NHMRC Clinical Research Working Group report 39 It should be noted that the Wills Report recommends the funding of research that has immediate effects on health outcomes and clinical practice, and/or economic benefits. Given the Commonwealth Government’s commitment to implement the recommendations of the Review, it would be desirable for the evaluation of clinical- research proposals to emphasise an assessment of the likely clinical impact of the research. Evaluation of the proponent’s track record should be broadened to include not just conventional research-output indicators (such as publications and citations), but also instances of previous research having been translated into clinical benefits. This point is included in application forms and guidelines for applicants and reviewers, but is not emphasised in evaluation processes. 4.4 Clinical trials and large-scale patient recruitment research 4.4.1 The spectrum of clinical trials and large-scale patient recruitment research Clinical trials and large-scale patient recruitment (CTLS) studies encompass a spectrum of different categories of research. At one end of the spectrum is the major multi-national clinical trial with a pharmaceutical-industry sponsor that funds all aspects of the study. At the other end of the spectrum is the large-scale, expensive observational (epidemiological) study in an area of strategic importance for the health system, but without any potential industry sponsor. Between these extreme examples, there is a range of observational and interventional studies for which industry support is variously limited or unavailable. These include trials of public-health programs, non-drug treatments, and evaluations of procedures, treatments or devices that do not have commercial backing.

Access to independent (non-industry) funding is important for research across this entire spectrum, for the following reasons. • Given the pivotal role of CTLS studies in generating the evidence for evidence- based practice, and the value accorded to evidence-based practice in the Australian health system, a mechanism for supporting such studies is an essential component in the implementation of Australian health policy. A national funding system is therefore needed for research on and evaluation of new health technologies and health care.

• Public funding of CTLS studies, and of the networks that support them, gives the studies a measure of independence and distance from industry, which may be essential for certain critical elements of the research. • Support from the NHMRC and other peer-reviewed research-funding agencies provides the credibility conferred by formal peer review, and ensures that the research is of high quality.

NHMRC Clinical Research Working Group report 40 • Support from the NHMRC and analogous Australian agencies gives the research an Australian stamp which may be very important, for example in promoting the implementation of the findings in the Australian health system. Even in studies which could be fully funded by an industry sponsor, the investigators may seek partial support from the NHMRC so the research is peer reviewed, is seen to be independent, and has an Australian identity. 4.4.2 Funding of CTLS research Currently, NHMRC grants are available to undertake large-scale studies such as clinical trials and epidemiological studies which involve extensive patient or subject recruitment and have a budget in excess of $300,000 in any one year or $750,000 in total funding requested. Funding for large-scale studies in 2000 totalled $1.9 million. In order to cope with the diversity represented in the spectrum of different types of CTLS research, the Working Group recommends that there be different mechanisms, criteria and levels of funding for different types of CTLS projects involving the NHMRC. The following categories should be considered.

• Large-scale clinical trials with industry sponsorship, or strong potential for sponsorship, for example, randomised controlled trials of drugs with a relevant commercial sponsor. For such studies, the Working Group recommends that: (a) direct NHMRC funding should be available to provide the Australian imprimateur and scientific credibility, but the funding should be limited financially to a sum that is within the range available for standard project grants; and (b) the NHMRC could additionally adopt a two-stage procedure in some circumstances to develop partnerships with other sources of funds, including industry or government (see below).

• Large-scale interventional or observational studies without industry sponsorship, and little potential for sponsorship, for example, comparisons of different types of prostheses for orthopaedic procedures, or large-scale occupational cohort studies in the transport industry. For these studies, the Working Group recommends that the NHMRC explore a number of mechanisms, as follows. (a) A two-stage procedure, in which the first stage is a scientific assessment of projects to determine whether their merit is such that they warrant support, whether or not the budget is beyond the capacity of NHMRC’s project-grants scheme. Projects of sufficient merit would proceed to a second stage in which the NHMRC would enter into discussion with the applicants and assist in the process of obtaining funding from other sources, including government and industry. The second Australian National Blood Pressure Study model exemplifies one avenue of funding from the Commonwealth Government, whereby the costs of visits to general practitioners over a 4-5 year period are chargeable against Medicare.

NHMRC Clinical Research Working Group report 41 (b) Funding through alternative NHMRC mechanisms such as national capacity building or Strategic Research Development Committee initiatives for studies in priority areas. (c) Partnerships between the NHMRC, other research agencies, industry, and State and/ or Commonwealth governments. An example is the Saline versus Albumin Fluid Evaluation (SAFE) Study, which is jointly funded by the NHMRC, Commonwealth, State and Territory governments, the New Zealand Health Research Council, and industry.

(d) Partnerships with funding agencies overseas for multi-national studies, utilising sources of funding in the other countries involved. This could be a two-stage procedure. (e) The establishment of a funding mechanism for research on, and the evaluation of, new health technologies and health care – as suggested by one respondent in the Working Group’s consultation. The rationale was that an investment of funds in high-quality research and evaluation of health technologies could be more important than the alternative continuing to fund the technologies in question, regardless of their effectiveness. In the first instance, it was suggested that one percent of expenditure on health technologies could be set aside by the Commonwealth Government for research and evaluation. A scheme could be established that either uses NHMRC committees, infrastructure and systems, or develops parallel systems which assure similar scientific quality and merit for each funded study.

4.4.3 NHMRC assessment processes for large-scale studies At present, applications for funding of CTLS research proposals are considered by individual GRPs, which have primary responsibility for deciding whether or not a project is funded. The Clinical Trials/ Large Scale Grants Committee (CTLSC) also considers these proposals, but has only an advisory role, not a decision-making role. Thus responsibility for deciding on the award of grants rests with groups that are discipline based. The GRPs tend to have a bias towards fundamental research, and they have insufficient funds for CTLS research. This arrangement militates against proper consideration of CTLS research proposals by the NHMRC. The problem is analogous to that of clinical-research project-grant applications described in section 4.3 above.

To overcome this problem, the Working Group proposes the establishment of a specific GRP for large clinical trials and other large-scale research proposals. The present CTLSC could evolve into this new GRP. From 2002, the new GRP could make the primary decision about applications for funding. Where it would be helpful, the new GRP could form linkages with, and obtain advice from, relevant content-area- specific GRPs on assignment to assessors. This effectively reverses the present arrangement. Clear criteria would be developed to define CTLS research, that is, to define the scope of research to be considered by the CTLS GRP.

NHMRC Clinical Research Working Group report 42 The new GRP would not have a specifically-allocated budget, but would have the same status (and the same call on funds) as other GRPs, including those responsible for the basic sciences. With regard to recommendations for funding, the CTLS GRP would have two options. • For studies with budgets falling within the normal range of project grants, the GRP would provide scientific assessment and grading exactly as is done by other GRPs, and thus would be directly involved in recommendations for funding. • For studies with budgets beyond the normal range, the GRP would adopt a two- stage procedure, separating those grants that warrant further consideration from those that do not, and engaging with the applicants in considering the various options outlined above, in close cooperation with the Office of the NHMRC. 4.5 Clinical trials centres 4.5.1 The need for clinical trials centre(s) While numerous clinical trials are being conducted in different types of research units throughout Australia, there are strong arguments for the continued existence of at least one national centre of expertise in clinical trials, along the lines of the NHMRC Centre for Clinical Trials in Sydney. As noted in section 4.4.1 above, clinical trials have a pivotal role in evidence-based practice, and given the value accorded to evidence-based practice in the Australian health system, a commitment at the national level to a capacity for clinical trials is of fundamental importance. This capacity must cover infrastructure, high-level expertise, methodological development and support, education and training, and the conduct or coordination of trials. Specifically, there is a need for: - leadership in, and capacity for, development and application of new methods in clinical trials; - a focus, or foci, of methodological expertise to which clinical trialists throughout Australia can refer; - centre(s) which can conduct or coordinate large clinical trials on a national scale; - centre(s) which can lead or coordinate international clinical trials, and which is internationally respected; - centre(s) which can serve as a node or regional coordinator in major international trials; - centre(s) which can dedicate resources to education, training, and mentorship; and - facilities which can bring together a variety of disciplines including health economics, biostatistics, and expertise in data management.

NHMRC Clinical Research Working Group report 43 4.5.2 Suggested arrangements The Working Group strongly recommends support for national clinical-trials centres (CTCs) through the NHMRC. At least two centres are recommended because: - there is increasing demand for clinical-trials capacity, and the single national centre that currently exists (the NHMRC Clinical Trials Centre in Sydney) is over-committed; - there is increasing demand for methodological advice on the design and conduct of clinical trials; - clinical-trials expertise is needed in diverse fields; and - there is a need for access to the services that a clinical-trials centre can provide in different parts of Australia.

The CTCs that are established should function as independent but collaborating units, possibly sharing aspirations, delivering joint training programs, having common ethics clearance processes, and participating in the clinical trials network described below. The NHMRC should also establish a clinical-trials network in which its own CTCs and other research groups undertaking large-scale clinical trials would actively participate. It should have a discrete secretariat which could be co-located with a research organisation conducting large-scale clinical trials. The network should have responsibility for promoting the formation of partnerships among Australian clinical- research organisations, in order to build critical mass and strengthen national capacity to (a) initiate major Australian and international studies in areas coinciding with national priorities, and (b) participate in major international projects initiated outside Australia.

If two or three CTCs are supported, they should provide for diversity in their fields of expertise, and be located in the different parts of the continent. For example, if there were two CTCs, one might have particular interest in cancer trials, while the other might specialise in cardiovascular, rheumatological or trauma-care trials. Their location should provide a geographical spread, or each CTC should have ‘branches’ in different parts of Australia. Each CTC should have a capacity to run or support a number of trials. This will create economies of scale, enabling each CTC to employ and make full use of the time of experts in such areas as economic analysis, high-level biostatistical analysis, and data management.

Each CTC should also act as a source of expertise for other units undertaking clinical trials, and should serve as a focus for training, thereby increasing national capacity for clinical trials. The CTCs will need two types of funding: (1) infrastructure funding; and (2) funding for projects.

NHMRC Clinical Research Working Group report 44 (1) Infrastructure funding: Infrastructure funding is needed not only to support the operations of CTCs, but also to support collaborations that are formed to undertake clinical trials. Items to be funded include insurance, data- management capacity, meetings of participants in multi-centre trials, and statistical analysis capacity. Specific emphasis should be given to the funding of clinical-trials networks. The funds should come predominantly from government, and funding should be at a level above that which could be obtained through the new NHMRC Program Grants scheme. The Commonwealth Government, possibly through the NHMRC, should be the primary source of infrastructure funding. The NHMRC should also have the role of broker. State governments with an interest in hosting a CTC could bid for it, with the bid adding funds and other resources to the funds available from the Commonwealth.

(2) Program and project funding: The CTCs should be eligible to compete for NHMRC Program and project grants. They should also seek funding from a wide range of other sources, including non-government organisations such as the Australian Cancer Society, the Clinical Oncological Society of Australia, the National Heart Foundation, and the Asthma Foundation, as well as the health and pharmaceutical industries. 4.6 Centres of Clinical Excellence in Hospital-based Research The existing Centres of Clinical Excellence (CCEs) program is an important mechanism for developing and sustaining clinical-research capacity in Australia. Inevitably, some posts which receive funding under the proposed CPR&D Scheme, described in section 4.2 above, would be located within CCEs. The Working Group recommends continuation of the CCE program, with the following modifications. • Each CCE should be funded for a sufficient period to allow sustainable development. Five years of funding in the first instance is essential, with the possibility of a second five-year cycle subject to satisfactory performance in the first cycle.

• The level of funding under the program should be substantially greater than that in the first round of awards, and accord with the importance of the award, implicit in the title ‘Centre of Clinical Excellence’. • The number of CCEs should be determined to ensure that the program is sustainable. The program should be structured to allow entry of new groups. CCEs funded for an initial five-year cycle should be eligible to apply for a second five-year cycle, but may be required to compete with new entrants. • As a criterion for funding, CCEs should demonstrate their capacity to provide training and education for clinical research, as well as mentorship for individuals undertaking clinical-research training. CCEs’ track record in training, education and mentorship should also be a criterion in the assessment of applications for extensions of funding.

NHMRC Clinical Research Working Group report 45 Consideration should be given to applications for Centres of Excellence in community-based research as well as in hospital-based research. 4.7 Office of the NHMRC The implementation of most of the Working Group’s recommendations for the development and enhancement of clinical research in Australia depends upon the NHMRC to serve a leadership or brokerage role. The performance of the NHMRC depends, in turn, upon the capacity of the Office of the NHMRC (ONHMRC) to serve catalytic, supportive and coordinating roles, and to provide documentation and follow-through on a very large range of initiatives. Members of the Working Group expressed dismay at the level of support available in the NHMRC to support its standing committee processes, let alone ad-hoc committees such as the Working Group. This raised serious doubts about the capacity of the NHMRC to support a broad-ranging program for the development of clinical research in Australia. The Working Group was concerned to ensure that a lack of capacity in the ONHMRC would not constrain the development of clinical research in the face of great opportunities and enthusiasm.

Accordingly, the Working Group recommended that the NHMRC should fund a full- time position for a senior clinical academic with a capacity for high-level liaison and program development (to be known the ‘Clinical Research Coordinator’). This position should be located within the ONHMRC. The Clinical Research Coordinator should fulfil a catalytic role in promoting and coordinating clinical research initiatives. He or she should take responsibility for the NHMRC’s initiatives in the training, recruitment and retention of clinical researchers, the provision of adequate infrastructure support, and the development of partnerships with governments, health services, teaching hospitals, universities, professional societies and colleges, and foundations.

The Working Group underlined the need for the ONHMRC to have sufficient infrastructural capacity to support the Clinical Research Coordinator and the initiatives for which he or she is responsible. The Working Group particularly highlighted the importance of ensuring that sufficient resources were available to prevent administrative service officers from becoming overloaded with diverse responsibilities amid competing priorities. The ONHMRC should dedicate administrative service officers to the development of clinical research, without any expectation that they would also serve other interests of the NHMRC. 4.8 Specific recommendations The Working Group formulated the following specific recommendations in relation to the maintenance of national capacity for clinical research.

NHMRC Clinical Research Working Group report 46 4.8.1 Establishment of the Clinical Practice Research and Development Scheme Recommendation 4A The NHMRC should promote and coordinate the development of a scheme whereby up to 600 clinician-researcher posts throughout Australia would be part-funded to an average extent of $50,000 per post per annum (indexed). These posts would be located in teaching hospitals and non-hospital settings, fostering clinical-research development in specialist disciplines as well as general practice, community-based mental-health practice, child health, and other population-based specialties. Funding for the scheme, to be known as the ‘Clinical Practice Research and Development Scheme’, would mainly be provided by Commonwealth, State and Territory Governments, with a contribution from the NHMRC, and possible contributions from other organisations such as the clinical colleges. The Scheme could be implemented over a ten-year period.

4.8.2 NHMRC Grants Review Panels for clinical research proposals Recommendation 4B The NHMRC should arrange for four or five of its Grants Review Panels to be designated as having an interest and expertise in clinical research. These panels should each have four or five clinician-researcher members who could assess and champion clinical-research applications appropriately. Clinical research applications should be channelled to these Grants Review Panels. 4.8.3 Support of clinical trials and large-scale patient recruitment (CTLS) research Recommendation 4C The NHMRC should continue to fund or part-fund high-quality clinical trials and large-scale patient-recruitment research. Provision should be made for the support of both clinical trials that have (or have the potential for) industry sponsorship, and large-scale interventional or observational studies without (and with little potential for) sponsorship from other sources.

- With regard to the former, direct NHMRC funding should be complementary to external funding, and normally limited to a sum that is within the range available for standard project grants. The contribution of NHMRC funding should place upon the research an Australian identity, and the involvement of NHMRC peer-review processes should ensure the rigour and credibility of the research. - With regard to the latter, mechanisms should be developed to obtain funds outside the standard NHMRC project grants scheme. Two-stage procedures should be used to assess proposals. The first stage should be a scientific assessment of the merit of the proposal. Projects of sufficient merit would proceed to the second stage, in which the NHMRC should assist applicants to obtain funding from other sources.

NHMRC Clinical Research Working Group report 47 Recommendation 4D A specific Grants Review Panel should be established for clinical trials and large- scale patient recruitment research applications. This Panel would have the same status, and the same call on funds, as other Grants Review Panels. It should make the primary decision about applications for funding, drawing where necessary on the expertise of other Grants Review Panels that have an interest in clinical research (see Recommendation 4B). 4.8.4 Clinical trials centres and a national clinical-trials network Recommendation 4E The NHMRC should support two or more clinical trials centres in Australia. These could function as independent but collaborating units, and they should participate in a national clinical-trials network (see Recommendation 4G). Between them the clinical trials centres should represent a variety of different fields of interest, and they should be located in different parts of the continent. Funding for the NHMRC clinical trials centres should cover infrastructure costs, and they should be eligible to compete for NHMRC Program and project funding.

Recommendation 4F The present NHMRC Clinical Trials Centre in Sydney should be eligible to apply for funding as one of the national clinical trials centres. Recommendation 4G The NHMRC should establish a clinical-trials network in which its own clinical trials centres would actively participate, as well as other research groups undertaking large- scale clinical trials. The network should have a discrete secretariat which could be co-located with a research organisation conducting large-scale clinical trials The network should have responsibility for promoting the formation of partnerships among Australian clinical research organisations, in order to build critical mass and strengthen national capacity to (a) initiate major Australian and international studies in areas coinciding with national priorities, and (b) strengthen national capacity to participate in major international projects initiated outside Australia. 4.8.5 NHMRC Centres of Clinical Excellence in Hospital-based Research Recommendation 4H The NHMRC should continue to fund the NHMRC Centres of Clinical Excellence program, with the following modifications.

- Each CCE should be supported for five years in the first instance. - There should be sufficient annual funding to warrant the title ‘Centre of Excellence’ – at least twice the level of funding provided for the first round of CCEs. - CCEs funded for an initial five-year cycle should be eligible to apply for a second five-year cycle, but may be required to compete with new entrants.

NHMRC Clinical Research Working Group report 48 - As a criterion for funding, CCEs should demonstrate their capacity to provide training and education for clinical research, as well as mentorship for individuals undertaking clinical-research training. CCEs’ track record in training, education and mentorship should also be a criterion in the assessment of applications for extensions of funding. - Consideration should be given to applications for Centres of Excellence in community-based clinical research as well as in hospital- based research.

4.8.6 Inclusion of clinical research in performance criteria for the accreditation of hospitals and health facilities Recommendation 4H Performance criteria for accreditation of hospitals and other health facilities should include measures relevant to clinical research, such as a certain proportion of patients entering clinical trials, a certain proportion of trainees completing higher degrees, and a track record of clinical-research publications and clinical trials approved. 4.8.7 NHMRC capacity for implementation of clinical research initiatives Recommendation 4I The NHMRC should fund a full-time position for a senior clinical academic with a capacity for high-level liaison and program development (to be known the ‘Clinical Research Coordinator’). This position should be located within the Office of the NHMRC. The Clinical Research Coordinator should fulfil a catalytic role in promoting and coordinating clinical research initiatives. He or she should take responsibility for the NHMRC’s initiatives in the training, recruitment and retention of clinical researchers, the provision of adequate infrastructure support, and the development of partnerships with governments, health services, teaching hospitals, universities, professional societies and colleges, and foundations. (See also Recommendation 3D.) Recommendation 4J The Office of the NHMRC should urgently be given sufficient resources so that it can acquire and retain an adequate infrastructure to serve standing committees and ad hoc committees, and can implement recommendations such as those set out in this report. Staff should be protected from an excessive workload that compromises their capacity to carry out secretariat functions effectively.

NHMRC Clinical Research Working Group report 49 5 Repositories for clinical research 5.1 Tissue banks 5.1.1 Definition and function of tissue banks A tissue bank is a storage facility containing tissue samples that are collected for use in research or in therapeutic applications. Depending on the nature and purpose of the tissue bank and the types of samples obtained, the tissue may be derived by surgical resection, biopsy, donation (e.g. of sperm), venesection (for collection of blood, plasma or serum), aspiration (e.g. of bone marrow), scraping, smear or brushing (e.g. of skin, buccal mucosa, or cervical mucosa), or washing (e.g. of bronchial mucosa), or it may be collected in the course of an autopsy.

The NHMRC Clinical Research Working Group confined its attention to tissue banks that collect human tissue for research purposes, especially clinical research. If (as argued below) tissue banks are to be registered and protocols, procedures and standards are to be invoked for their management, it becomes necessary to specify criteria for determining whether any given collection of tissue constitutes a tissue bank. A key criterion is the intent of the collection. Many existing collections of tissue – such as stained histological sections on microscope slides retained by pathologists for confirmatory purposes – are unlikely to be identified as tissue banks, although they could potentially be used in clinical research. The essential components of a tissue bank are: - the tissue samples, properly prepared and stored; - a mechanism for linking each tissue sample to clinical data on the individual from whom the sample was obtained; - a catalogue and index system; and - processes for giving approved researchers access to tissue samples and related clinical data, including follow-up information on clinical outcomes. Linkage of tissue samples to clinical data is crucial for the use of tissue banks in clinical research. The clinical data may comprise records held in the tissue bank, or there may be a mechanism for linking tissue samples to routine patient records, such as hospital records. A powerful option is to link the tissue bank to a disease register (for example, to link a bank of surgically-resected tumour tissue to a cancer register), as this enables follow-up information on medium- and long-term outcomes to be obtained.

5.1.2 The need for standardisation Although research using human tissue is widespread, relatively few fully-developed tissue banks are in operation in Australia. Those that exist have mostly been established and maintained on a local or institutional basis, meeting the needs of particular groups of investigators, and following protocols that have been devised, perhaps idiosyncratically, at a local or institutional level. Practically no effort has

NHMRC Clinical Research Working Group report 50 been made to coordinate tissue banks that exist for similar purposes in different places. No concerted attempt has been made to standardise tissue collection, storage methods, or clinical profiles, and no guidance on how to run a tissue bank is available at a statewide or national level. Only a few centralised tissue banks exist or are under development. These include a bank of surgically-resected tumour tissue that is maintained by the Peter MacCallum Institute in Melbourne, and a proposal for a centralised Western Australian bank of surgically-resected tumour tissue. The NHMRC currently has no formal role or position in the establishment, development, funding or maintenance of tissue banks.

The value of and need for a considered national approach to the development and maintainance of tissue banks are increasingly recognised. Centralised tissue banks and networks of tissue banks that collect similar types of tissue offer obvious economies of scale, and can enable larger studies (particularly studies requiring tissues with very specific types of pathology) to be undertaken and completed more rapidly. However, for centralised tissue banks and networks to operate effectively, standardised procedures must be developed and adopted for the following: - the collection, handling and storage of tissue samples; - the collection and documentation of clinical data, including follow-up outcome data; - the indexing and cataloguing of samples; - approaches for seeking consent to collect and retain tissue and use it for research purposes (see section 5.1.3 below); - the provision of security systems for maintaining privacy and confidentialty (section 5.1.3); - mechanisms for giving approved researchers rapid access to the tissue samples and associated clinical data; and - determining management structures and processes. The NHMRC should take a leadership role in convening a regular forum to make recommendations on these standardised procedures, document them, and update them. This forum should report to the Research Committee, and could constitute a sub- committee of the Research Committee.

5.1.3 Ethical considerations, privacy and confidentiality Agreement is also needed on procedures to resolve ethical concerns about the retention of human tissue and its use in research. These concerns focus on: - the very fact that tissue is retained, and - the linkage of tissue-bank samples to clinical data on the individuals from whom they were derived. Several ethnic, cultural and religious groups in the Australian community strongly oppose the retention of tissue as a matter of principle. In addition, throughout the Australian community, some individuals object to the retention of their own tissue or tissue collected from family members. The strength of feeling may vary with the nature and size of the tissue sample retained. For example, many people would consider that a needle-biopsy specimen or a smear on a microscope slide does not have the same significance as a whole organ or a mass of resected tissue. The

NHMRC Clinical Research Working Group report 51 retention of post-mortem material and tissue derived from stillbirths raises particular concerns. The spectrum of attitudes about the retention of human tissue underlines the need for widely-endorsed procedures that meet ethical requirements and fulfil community expectations. There is a need for specification of: - procedures for obtaining and recording consent, - situations where consent is not required, - procedures for maintaining privacy and confidentiality, and - procedures for obtaining access to follow-up data on patients (e.g. data on medium- and long-term clinical outcomes).

Guidance is needed on these matters in relation to both: - the collection and retention of tissue and associated clinical data in tissue banks, and - the release of samples and clinical data from tissue banks for research projects. Following from the leadership role proposed for the NHMRC in relation to the development of standardised procedures for tissue banks, the Australian Health Ethics Committee (AHEC) of the NHMRC should lead debate and produce guidelines on ethical and privacy issues relating to tissue banks. 5.1.4 Registration of tissue banks Individual researchers may not know of the existence of all tissue banks from which they could potentially draw samples for study. The development of effective networks of tissue banks could be enhanced by a system of registration, whereby tissue banks that follow standardised procedures (including recommended processes for privacy and ethics) could be enlisted and described in a common database. The NHMRC could sponsor the development and maintenance of this database of tissue banks, and it could be accessible to all researchers through the NHMRC website. 5.1.5 Resources for the development and maintenance of tissue banks The NHMRC’s role in relation to tissue banks, identified in sections 5.1.2 – 5.1.4, is to provide leadership and coordination, with particular emphasis on the standardisation of operational policies and procedures and the development of networks. There is no expectation that the NHMRC would become a major funder of tissue banks. Indeed, one of the major examples of a centralised tissue bank, the proposed Western Australian Tissue Bank, is funded by the Health Department of Western Australia, with contributions from hospitals, universities, clinicians, and others. However, as part of its leadership role, the NHMRC should help to identify sources of funding for tissue banks. The NHMRC could also assist in promoting the development of tissue banks by soliciting proposals for research projects (particularly clinical-research projects) that make use of tissue banks.

NHMRC Clinical Research Working Group report 52 5.2 Disease registers 5.2.1 Definition and functions A disease register is a systematic collection of data on all cases of a particular disease in a population (population-based register) or in a clinical service (clinic- or hospital- based register). The terms ‘registry’ and ‘register’ tend to be used interchangeably. In this report, ‘register’ refers to the repository of accumulated data, while ‘registry’ refers to the organisation that runs the register.

Population-based disease registries usually collect cross-sectional and longitudinal data for epidemiological monitoring of disease occurrence, care processes, and outcomes. Data items typically encompass demographic characteristics of people with the disease, aspects of the disease process (for example, cancer registries may record data on the primary site and histopathology of the tumour), and selected major outcomes (particularly survival). Population-based registers may also contain information on aspects of initial and follow-up clinical management. In addition to their use in cross-sectional and longitudinal epidemiological monitoring, population- based registers are valuable sources of data for epidemiological research. Their potential application in clinical research and in the monitoring of treatment depends on the amount of clinical detail that can be ascertained reliably using population- based ascertainment methods. Some population-based registers are also used to generate patient-reminder systems (for example, the Australian Childhood Immunisation Register, and State and Territory Pap test registers). Clinic- or hospital-based disease registries usually collect much more detail than population-based registries on the disease process, primary treatment, subsequent treatment, disease progression, and short-term outcomes, as well as longer-term outcomes. Their usual primary intent is to provide data for monitoring the quality of services, for resource and planning purposes, and for research purposes. In their quality-assurance role, disease registers can show actual patterns of treatment for comparison with treatment guidelines, and they can describe outcomes in relation to expectations (taking account of disease severity and other prognostic indicators). For clinical-audit purposes, they also enable identification of patients who have received unusual treatment and those who have poor outcomes. Clinic- or hospital-based disease registers can contain, or can be linked with, substantial amounts of clinical information for studies on such topics as detailed aspects of treatment and quality of life. They also have the potential to be linked with tissue banks. Thus, for example, the molecular biology of tumour tissue (from a tissue bank) can be studied in relation to clinical markers of potential prognostic importance (as recorded in a disease register).

In addition to population-based and clinic- or hospital-based disease registers, other types of registers exist or have been proposed. Examples include registers of implanted devices, which retain data on and follow up patients with particular types of prostheses such as heart valves or joints. These registers enable outcomes to be studied, adverse events to be flagged, and patients to be recalled if serious instances of device failure occur.

NHMRC Clinical Research Working Group report 53 5.2.2 Mechanisms for support and coordination of disease registers The distinction between quality-assurance projects, epidemiological monitoring, and research projects is often blurred. Both population-based and clinic- or hospital-based disease registers are costly to set up and run, and the expense can usually be justified only if they fulfil some combination of quality-assurance, epidemiological- monitoring, and research purposes. To date the NHMRC has had very little involvement in disease registers of any type. Most disease registries in Australia are funded by Commonwealth, State and Territory governments, and are run either by health departments or government instrumentalities such as the Australian Institute of Health and Welfare (AIHW), or on behalf of health departments (under contractual arrangements) by non-government organisations, universities, or research institutes. The small number of hospital-based disease registries that exist in Australia are operated within clinical departments of teaching hospitals.

The coordination that exists among disease registers throughout Australia is due largely to the efforts of peak national bodies such as Australian Cancer Society, which has provided a forum for harmonisation of the separate data-collection efforts of individual State- and Territory-based cancer registries. The AIHW has also had an important coordinating and leadership role. For example, the AIHW National Perinatal Statistics Unit, located at the University of New South Wales, assembles national data on congenital malformations from the birth-defects registers that operate in some States, and from other sources in other States and Territories. The terms of reference of the NHMRC Clinical Research Working Group imply a focus on clinical-research aspects of disease registers. The NHMRC Clinical Research Working Group reaffirmed the value of disease registers, and emphasised the enormous potential contribution of clinic- or hospital-based registers in clinical research. A full review of disease registers was beyond the scope of the Working Group. Rather, the key question addressed in this report is as follows: should the NHMRC have a role in the development of disease registers, and if so, what should that role be?

5.2.3 Issues in the development and operation of disease registers While some of the following points are relevant to all types of disease registers and registries, they apply particularly to clinic- and hospital-based registries. The success or failure of disease registries depends on whether they lead to changes in clinical practice and better outcomes for patients. Their effectiveness, in turn, depends upon the following factors. • Support and input from the medical community, hospital and health-service management, health departments, and special-interest organisations such as cancer councils.

• Secure, long-term funding.

NHMRC Clinical Research Working Group report 54 • Realistic goals and objectives, determined in consultation with clinicians, health services, and the community. • Data collection that fulfils the goals and objectives, and is not excessive. • Quality-control processes, covering the acquisition of data, ethical processes, and systems for ensuring privacy and confidentiality of data. • Timeliness of data collection and reporting, with data being made available rapidly for research purposes.

• Feedback and implementation in practice of information derived from the register, and use of register data to its full potential in research. The importance of secure, long-term funding at a sufficient level cannot be over- emphasised. Once established, disease registers bring a particular responsibility for continuing support, and they are notoriously labour intensive. Stable resources are especially needed to attract and retain qualified, experienced personnel. In particular, an expert data manager has a central role in the success of a disease register. Contemporary pressures on health-system funding, discussed in Chapter 1, make it difficult for health services to fund positions for data managers. It is most important that data management is not relegated to inexperienced individuals unfamiliar with registry processes. Resources are also needed to establish and maintain high-quality information-technology systems, and for the design and development of the register database.

As is the case with tissue banks (see section 5.1.2 above), there is a need for standardisation of data collection among comparable disease registers in different institutions and localities, so that data can be pooled. Efforts at standardisation have been made among the major population-based disease registers throughout Australia, and some hospital-based cancer registries (such as those in South Australia) also have standardised data collections. With regard to research, the potential utility of disease registers has not been fully explored. Linkage with tissue banks offers some very exciting possibilities. Disease registers also offer the potential for highly efficient collaborative clinical trials, with subjects being identified and followed up through the registers. The feasibility of such research depends upon coordination and standardisation among registries, and upon resolution of ethical considerations. It also depends upon the timeliness of operation of the registers, so that the registers ‘feed’ cases into the clinical trial, rather than the reverse.

5.2.4 Possible roles of the NHMRC in relation to disease registers The role of the NHMRC should be tempered by the fact that most population-based disease registers in Australia are funded and managed (directly or indirectly) by Commonwealth, State and Territory health departments. Few clinic- and hospital- based disease registers are in operation. The NHMRC should take a leading role in

NHMRC Clinical Research Working Group report 55 promoting their development and assessing their contribution to the improvement of clinical practice and patient outcomes. However, the NHMRC cannot be expected to become a major funder of disease registers. Specifically, the NHMRC should take a leadership role in facilitating the development and support of clinic- and hospital-based disease registers. This could include the following: • A review of clinic- and hospital-based disease registers that currently operate or are planned, aiming to determine their scope, goals and objectives, their actual and potential utility with respect to research and other outputs, how they are funded, and factors that impede and factors that could enhance their effectiveness; and to make recommendations arising from these inquiries.

• In conjunction with the National Health Priorities Action Council, a review to determine which disease conditions warrant the development of disease registers. • Identification of opportunities for proponents of disease registers to obtain stable funding. • Sponsorship of a regular national forum for methodological development of disease registers and register-based research, standardisation of data collection processes, and the development of linkages between tissue banks and disease registers.

• Development of ethical guidance and privacy and confidentiality standards for disease registers. • Solicitation of proposals for grants to undertake research projects using disease- register data, particularly favouring demonstration projects which use innovative methods, and which draw on expertise of other NHMRC-supported entities such as clinical trials centres. 5.3 Registers of clinical trials While the proliferation of clinical trials in recent years has made a major contribution to the knowledge base of clinical practice, some community and professional concerns have emerged about the funding, conduct and monitoring of trials. These concerns have been triggered by incidents (often widely publicised) in which there have been allegations of conflicts of interest among funders of trials or researchers, and/or questions about the adequacy of consent processes and other ethical issues. Individuals often express willingness or even a wish to participate in trials. However, they expect to be fully informed when clinicians recommend medications that are under trial, and they also expect to be informed about potential vested interests associated with trials. The demand for openness about all aspects of trials is increasing.

NHMRC Clinical Research Working Group report 56 Researchers who conduct clinical trials are also demanding more information about trials other than their own, including trials that are planned, trials in progress, and trials that have been completed but not published. This information helps to avoid duplication, and can enable coordination in the development of trials, making systematic reviews and meta-analyses feasible or more efficient. Public, professional and researcher requirements for information about clinical trials has led to proposals for the establishment of a national register of clinical trials. The register would be accessible by members of the public as well as those with a professional interest in trials. Users of the register could find out about current trials and how to obtain access to them. There would be a need to develop procedures for protecting intellectual property, including information that is considered to be ‘commercial-in-confidence’.

Given its proposed role in developing clinical trials centres and promoting clinical trials and large-scale patient-recruitment research, the NHMRC is well placed to assess the potential value of a national register of clinical trials and take a leadership role in its development. The NHMRC should work with State and Territory health authorities to determine how a national register should operate, and how it should be funded. A working group examining these questions should contain representatives of the clinical trials centre(s), the Therapeutic Goods Administration, the Australian Pharmaceutical Manufacturers’ Association, and consumer organisations, as well as State and Territory health departments and the NHMRC (including AHEC). 5.4 Specific recommendations 5.4.1 Development of tissue banks Recommendation 5A The NHMRC should take a leadership role in a national approach to the development of human tissue banks, including centralised tissue banks and networks of tissue banks that collect similar types of tissue banks. As part of its leadership role, NHMRC should help to identify sources of funding for tissue banks. It should also assist in promoting the development of tissue banks by soliciting proposals for research projects that make use of tissue banks.

Recommendation 5B The NHMRC should convene a regular forum to make recommendations on standardised procedures for the management and operation of tissue banks. This forum should be constituted as a sub-committee of the Research Committee. Recommendation 5C The Australian Health Ethics Committee of the NHMRC should lead debate on ethical and privacy issues relating to tissue banks, and should coordinate the production of guidelines on these issues.

NHMRC Clinical Research Working Group report 57 5.4.2 Development of disease registers Recommendation 5D The NHMRC should take a leading role in promoting the development of disease registers and in assessing their contribution to the improvement of clinical practice and patient outcomes, with a particular emphasis on clinic- and hospital-based registers. Recommendation 5E The NHMRC should carry out a review of clinic- and hospital-based disease registers that currently operate or are planned, aiming to determine their scope, goals and objectives, their actual and potential utility with respect to research and other outputs, how they are funded, and factors that impede and factors that could enhance their effectiveness. In conjunction with the National Health Priorities Action Council and the National Institute of Clinical Studies, the NHMRC should also carry out a review to identify the disease conditions that warrant the development of disease registers. Arising from these reviews, the NHMRC should make recommendations on the development of clinic- and hospital-based disease registers, and identify opportunities for proponents of disease registers to obtain funding for the implementation of the recommendations.

Recommendation 5F The NHMRC should sponsor a regular national forum for methodological development of disease registers and register-based research, standardisation of data- collection processes, and the development of linkages between tissue banks and disease registers. Recommendation 5G The Australian Health Ethics Committee of the NHMRC should develop ethical guidance and privacy and confidentiality standards for disease registers. Recommendation 5H The NHMRC should solicit proposals for project grants to undertake research projects that use disease-register data, particularly favouring demonstration projects which use innovative methods, and which draw on expertise of other NHMRC-supported entities such as clinical trials centres.

5.4.3 Development of a national register of clinical trials Recommendation 5I The NHMRC should work with State and Territory health authorities to determine how a national register should operate, and how it should be funded. A working group of the Research Committee should be formed to examine these questions. It should contain representatives of the Therapeutic Goods Administration, the National Institute of Clinical Studies, clinical trials centre(s), the Australian Pharmaceutical Manufacturers’ Association, and consumer organisations, as well as the NHMRC (including the Australian Health Ethics Committee), and State and Territory health departments.

NHMRC Clinical Research Working Group report 58 Appendix 1: Consultation of the health and medical research community Introduction In June-July 2001, the Office of the NHMRC, on behalf of the Clinical Research Working Group, sent an e-mail to all Australian residents on its research list-server. The e-mail informed recipients of the establishment and purpose of the Working Group, and invited them to respond to a simple questionnaire described below. The Working Group conceived the e-mail as a consultation mechanism, not as a representative survey of researchers.

The aims of this consultation were: • to inform recipients about the planned activities of the Working Group, and to provide an opportunity for recipients to comment on these activities; • to find out what clinical researchers think about the current status of clinical research in Australia; • to collect ideas and suggestions for the Working Group on how Australian clinical research can be improved and promoted; and • to obtain feedback within the priority areas already identified by the Working Group.

THE QUESTIONS The first item was an open question, designed to elicit general comments about clinical research: Please enter any comments that you would like to make about clinical research in the space below. The second item sought respondents’ comments on specific topics within the Working Group’s terms of reference: In addition, your views on the areas listed below, which are of particular interest to the NHMRC, would be most welcome. - Infrastructure and funding for clinical research - Training of clinical researchers - Recruitment, retention and career development of clinical researchers - Support of clinical trials and other large-scale studies - Collaborations and partnerships that enhance the capacity and effectiveness of clinician-researchers - Development of disease registers and tissue banks Finally, the e-mail contained four closed questions asking respondents to provide some information about themselves, in order to help with the sorting of the responses.

NHMRC Clinical Research Working Group report 59 The questions were: • Are you currently involved in research? (yes / no) • Are you currently involved in (clinical research / other forms of research)? • Do you consider yourself to be (an early-career researcher / an established or mid- career researcher / a senior researcher)? • Are you currently involved in clinical practice in Australia? (yes / no) RESULTS The consultation process generated 168 e-mail replies to the automated database by the closing date (31 July 2001) and 15 written responses. Responses ranged from a single sentence (i.e. a suggestion to improve clinical research training or a general expression of support for the initiative) to detailed three-page commentaries. The replies to the two items in the e-mail were collated as follows. • General comments about clinical research in Australia (the first item) were categorised into ‘key themes’, given below. The issues addressed within each of these themes overlap significantly.

• Specific points made in relation to the second item are listed under the topics identified in the second item. Of the 168 individuals who responded to the e-mail, 97% indicated that they were currently involved in research. Of these, 93% were involved in clinical research, and 69% in other forms of research (obviously a proportion were involved in clinical and other forms of research). Of the 168 respondents, 29% characterised themselves as early-career researchers, 38% as established or mid-career researchers, and 32% as senior researchers. Sixty-eight percent said that they were currently involved in clinical practice in Australia.

THE FIRST ITEM: KEY THEMES Disincentives and barriers to clinical research There appeared to be overall agreement that clinical research in Australia was difficult and that its quantity and quality should be enhanced. The problem was primarily identified as the current ‘ethos’ of both health-service and tertiary-education institutions, with research by promising people being hindered rather than supported. Consequently, clinical researchers are rapidly discouraged and give up. Clinical research was regarded as ‘an endangered species’ and ‘a very difficult career path in Australia’.

Respondents often identified disincentives and barriers faced by themselves and their colleagues. These were grouped as follows: - lack of time;

NHMRC Clinical Research Working Group report 60 - inadequate funding; - low levels of research expertise; - lack of infrastructure and support; - inadequate recognition and reimbursement; - NHMRC funding procedures and criteria. Lack of time The most significant barrier to the conduct of clinical research for many practising clinicians was reported to be the lack of dedicated research time. This seems to have become an increasing problem over the 20 years, as clinical workloads and demands for patient throughput have increased.

Clinicians also identified changed attitudes towards family commitments. The traditional clinical researcher stereotype was described as a man who worked every evening and weekend on research, while his wife looked after all the domestic affairs. In contrast, the typical picture today is a two-career couple, with both partners wishing to spend time with their family. Clinical researchers must balance the triangle of clinical work (which ‘pays the bills’), family life (which is now given greater priority), and research (which is currently perceived as difficult, poorly paid, lacking a definable career path, and unsupported by incentives or acknowledgement from the health system or the research world).

Inadequate funding Most respondents asserted that clinical research is inadequately funded in Australia (apart from drug trials funded by the pharmaceutical industry). Independent funding sources, such as the NHMRC, were perceived to concentrate their resources on basic sciences. Many respondents commented on the need for dedicated funds to be allocated to clinical research, with clinical researchers acting as reviewers of the grant proposals. Low levels of research expertise Respondents acknowledged that there were excellent clinical researchers in Australia, but noted that many clinicians who undertook research had very little formal research training, let alone clinical-research training. As a result much of the clinical research done in Australia was poorly designed, badly conducted and inappropriately analysed. The methods and knowledge needed for today’s research were recognised as being increasingly separate from those required for clinical practice. Respondents observed the increasing difficulty of participating at a high level in clinical research and clinical practice, unless substantial additional training and support were forthcoming. As one respondent commented, ‘The traditional model of the clinician doing a bit of research on the side is now unlikely to generate world class research…the specific role of individuals with clinical and research qualifications needs to be acknowledged and supported in a new model.’

NHMRC Clinical Research Working Group report 61 Respondents also felt that funding constraints in universities, health-service budget pressures, and increases in clinical loads in hospitals were hindering collaborations between University research scientists and clinicians that would improve the quality of clinical research. Lack of infrastructure and support Clinical research was described as something done against the odds by the truly committed, rather than as a vital activity that was encouraged and supported within the Australian health system.

Inadequate recognition and reimbursement Respondents commented that potential clinical researchers lacked motivation to overcome barriers to clinical research because clinical research was not recognised as a worthwhile activity by their peers or employers. Clinical research was also described as very poorly paid compared to clinical work generally, but particularly compared to private clinical practice. Clinicians who move into private practice are even less likely to participate in clinical research. NHMRC funding procedures and criteria Respondents had a very strong perception that the NHMRC has not placed enough emphasis or importance on clinical research as a priority area. Respondents expressed the view that the NHMRC did not recognise clinical research as legitimate or ‘real’ research.

Respondents also commented that there was too much emphasis in NHMRC funding criteria on the chief investigator’s research track record, rather than research potential and the quality of the research proposal. There was also an exclusive focus on research in the last five years. These factors militated against successful grant applications from both new investigators and senior clinicians who had not recently done research. There were several comments that the current NHMRC criteria for ‘rigour’ do not support holistic multi-method research designs which can capture both qualitative and quantitative data. Multi-method and multi-disciplinary research was described as essential in the clinical setting.

Several respondents recommended that NHMRC should appoint more grant- application reviewers who have experience in clinical research.

NHMRC Clinical Research Working Group report 62 Sponsorship and influence by the pharmaceutical industry The strongest theme to emerge from participants’ general comments was the significant concern about the domination of clinical research in Australia by the pharmaceutical industry. Most industry-sponsored research was perceived as a pre-marketing exercise for new products rather than ‘real’, credible or useful research. There was a strong perception that industry-sponsored trials rarely asked the important clinically-pertinent questions. Participants identified the need for more investigator-initiated, independently- funded research, which would address questions asked by clinicians and their patients. Drug trials were, however, recognised as a major source of funding. Over time, earnings associated with trials provided an opportunity for clinical researchers to build up reserves of funds for research infrastructure within their institutions. These resources were sometimes used to support investigator-initiated research addressing clinically-important issues.

Lack of innovation and interdisciplinary collaboration Perceptions about inadequate opportunities to obtain funding for independent, investigator-driven research, particularly for young and creative researchers, resulted in many comments about a lack of truly innovative research in Australia. There was a sense that most of the good ideas generated by clinical researchers have to be taken overseas for development, testing and application. Australia’s best research graduates move to US or UK institutions due limited opportunities to undertake new and innovative research locally.

Australian clinical research was also criticised for being too narrow in its focus (too many drug trials) and too biomedically oriented. A lack of funding for inter- disciplinary research was observed. Need for applied ‘translational’ research Many respondents commented on the lack of, and serious need for, research that addresses the translation of developments within basic science and medical technology into applied clinical practice. There were many comments that research funding in Australia over-emphasises basic biomedical sciences and drug trials, neglecting research that examines whether and how new ideas can be translated into practice.

NHMRC Clinical Research Working Group report 63 SECOND ITEM: COMMENTS ON SPECIFIC ISSUES Infrastructure and funding for clinical research One of the strongest and most frequent criticisms was the inadequate funding of investigator-driven studies (as opposed to pharmaceutical industry-driven studies) that answer important clinical questions. The most significant barrier to clinical research that is independent of industry is the lack of supporting staff, infrastructure and other funding. The lack of infrastructure and funding for clinical research was primarily attributed to the fact that health services and hospitals do not identify research as their responsibility, and universities are under too much financial pressure to undertake the responsibility of clinically-based research. Thus clinical research falls between the health care and university systems.

Despite criticism, the value of pharmaceutical-industry funding of clinical research was recognised. It enabled clinical researchers to accumulate reserves of funding for infrastructure. These reserves were often the only source of support for clinical research that was not of immediate commercial interest. Respondents commented on the excessively narrow interpretation of research- infrastructure requirements in many infrastructure grants. They pointed out the need to fund the following elements: • Staff and other resources dedicated to coordinating clinical research; • Information exchange about research activities around the country; • Clinical-service back-up for clinicians who wish to be involved in research; • Local and national grants, sponsorship, scholarships and research positions to provide opportunities for young clinical researchers to obtain experience and training; • Dedicated research units, e.g. metabolic research units; • Research nursing staff; • Study coordinators; • Data managers; • Data analysts. Overall, there was absolutely no sense that clinical research was systematically supported, encouraged or identified as a valued or important activity within the Australian health system. Several participants pointed to the dedicated programs of clinical research in the US and the UK as marked contrasts to the situation here. Recommendations Translational research was particularly identified as worthwhile area for the NHMRC to support with infrastructure funding.

NHMRC Clinical Research Working Group report 64 The NHMRC should act as a political advocate for clinical research, aiming to achieve support at State level and, subsequently, allocation of funding for clinical- research infrastructure at the hospital level. Training of clinical researchers Training was required for clinical researchers in the following areas: • medical statistics • research design • clinical epidemiology • qualitative research • ethics • multi-disciplinary research • design of clinical report forms and questionnaires • database development Current Australian clinical-research training was perceived as haphazard, with most clinicians who undertake research training working in laboratory-based sciences. There was a perception of a ‘brain drain’ to North America and Europe of those who show the most potential during clinical-research training, because of a lack of opportunity or support to further their career in Australia. Conversely, much of the clinical research currently done in Australia is done by doctors with no formal clinical research training.

Recruitment, retention and career development of clinical researchers ‘Career development is lousy – you do a research training and get a quarter of the salary of your non-research-oriented clinical colleagues, and then, if you’re lucky, at the end you get an academic job where you do twice the work for half the pay, and are regarded in the hospitals either as an eccentricity or a liability.’ Respondents pointed out that the lack of a systematic, organised approach to promoting, monitoring, facilitating, funding and evaluating clinical research in Australia. Clinical research was perceived as having no value for hospital managers, administrators or governments. Indeed clinicians who conducted research were seen (within the health services) as taking time away from their ‘real’ jobs of dealing with clinical workloads.

Respondents noted that remuneration and job security all tend to favour clinical practice rather than clinical research – they insisted that this must be equalised or clinical researchers could not be recruited or retained. Finding funds for post-doctoral positions in clinical research was described as being so difficult that the most promising graduates became less interested in higher-degree research-based programs than obtaining specialist clinical training. No incentive

NHMRC Clinical Research Working Group report 65 existed to obtain clinical research qualifications at an early career stage, and job security was often reduced as a result of pursuing research qualifications. Respondents highlighted the need to include clinical research as a performance indicator for all senior clinical staff (i.e. an knowledge of research methods and participation in clinical research should be expected, supported and funded by health service employers and should be a requirement for membership of professional colleges).

Respondents also noted the lack of a career path for clinical researchers within the health system, compared to clinical career paths and university career paths. This was the case for medical and allied health researchers. Support of clinical trials and other large scale studies There was much comment on the domination of clinical research in Australia by the pharmaceutical industry. Respondents called for more support of clinical trials that answered real clinical questions valued by practitioners and patients, rather than trials that are conducted to support the marketing of new drugs.

Collaborations and partnerships Respondents identified the following important partnerships: • Clinicians and university-based researchers with methodological expertise, such as epidemiologists and statisticians; • Medical clinicians and other allied health clinical researchers, particularly those with social and behavioural science and anthropology skills; • Clinical researchers in major teaching hospitals and those in rural or remote areas; • The public sector, universities and private health services; • National and international clinical research groups. Development of disease registers and tissue banks The main messages were as follows.

• Tissue banks and disease registers were supported by the respondents. • Australia should have done a better job at establishing and coordinating tissue banks and disease registers years ago. • Restrictive privacy legislation has been a major barrier. • Lack of national collaboration and agreement is another major barrier. • Funding is often short term and piecemeal. Researchers often struggle to establish national tissue banks by applying for small amounts of local funding. Initiatives often fail to achieve their potential due to a lack of national coordination, communication and long term stable funding.

NHMRC Clinical Research Working Group report 66 Appendix 2: Examples of clinical research initiatives undertaken by professional organisations As noted in section 1.4, the Chair of the Working Group wrote to the heads of some 70 educational bodies, professional societies and other agencies throughout Australia that have an interest in clinical research. In his letter, he asked for: - copies of relevant reports and/or relevant analyses and action plans; - views on priority issues that the Working Group should address, and recommendations for action to enhance the quality and vigour of clinical research in Australia; and - views on the development of an ongoing mechanism whereby all agencies concerned with the support of clinical research and training of clinical researchers could work together.

The letter was sent to Deans of Faculties of Medicine, Presidents of Medical Colleges and special societies, State and Territory Chief Medical Officers, and the heads of some other non-government organisations that support clinical research. The following table summarises some major examples of responses that indicate the types of support provided for clinical research from: - professional organisations and Colleges; - non-government organisations and special-interest groups; and - health services, hospitals and universities.

NHMRC Clinical Research Working Group report 67 Professional organisations and Colleges Organisation Clinical research initiatives Other research training Royal Australasian College Physicians, Research Foundation administered by RACP Research Advisory Committee. In 2001 a joint committee of the RACP and ANZ Society of Nephrology will award a $250,000 grant to support a multicentre clinical trial and provide higher level training for a Fellow in epidemiology and clinical trial development. A$1 million allocated to Fellows and advanced trainees. In 2001, 30 awards available to projects in internal medicine: paediatrics, child health, public health and epidemiology (not necessarily in clinical research).

Australasian College of Physical Scientists and Engineers in Medicine Support translational and clinical research projects Training program for clinical work, but not explicitly in clinical research Royal Australasian College of Surgeons RACS Foundation, established 1982, currently provides $1.5m annually in research scholarships. Directed by College’s Board of Surgical Research, and Professor of Surgical Sciences. Current debate on whether funds should be allocated to 35-40 individual peer- reviewed scholarships based on merit, or funds targeted to an agreed area of need. Activities to facilitate research - Australasian Surgical Research Network (web-based details on research projects) - Australasian Surgical Research Expos Training activities - College Fellowships and Scholarships (30 people funded and trained) - Surgical Scientist Program (new) promoting a combined PhD/FRACS qualification – currently 12 people - CLEAR Worshops (Critical Literature Evaluation and Research).

- Australian Safety and Efficacy Register of New Interventional Procedures – Surgical. A Commonwealth-funded unit within the College, based in Adelaide. Conducts systematic reviews, procedure assessment and guidelines. Three-year pilot completed 2000, Commonwealth funding awarded for another 4 years. (Provide research electives for medical students. 3 students in 2000-2001.)

NHMRC Clinical Research Working Group report 68 Royal Australian and New Zealand College of Radiologists Primary focus is on clinical training. However, does have a research fund for several individual research projects per year (seeding grants – types of research and funds not specified). Research Funds for projects in a variety of fields: 1997/8: $58,570 (total) 4 projects 1998/9: $39,741 to 5 projects 1999/0: $59,200 to 5 projects 2000/1: $85,630 to 6 projects 2001/2: $ 106,147 to 10 projects Currently, once exams have been completed, advanced trainees can do clinical or basic research in their 5th year. College is keen to expand these trainee positions. Royal Australian College of General Practitioners, Research and Practice Support Directorate Pfizer sponsored Cadiovascular Research Grants scheme: $300,000 over 3 years. Centre for National Research on Disability and Rehabilitation Medicine $50,000 Research Fellowship recently advertised. Annual Registrar Research Workshop: 39 attended in 2001 (developing research questions).

NHMRC Clinical Research Working Group report 69 Non-government organisations and special-interest groups Organisation Clinical research initiatives Other research training Anti-Cancer Council of Victoria, Centre for Clinical Research in Cancer and Victorian Cooperative Oncology Group 2001 budget for clinical trials was $595,000, awarded through the Cancer Trials Management Scheme and Clinical Trials Office. Additional $294,000 received for trials from DHS Victoria and Victoria Breast Cancer Research Consortium.

Cancer Foundation of Western Australia Scientific Advisory Committee has prepared a report that promotes clinical research (not sighted) Australian New Zealand Breast Cancer Trials Group A$1 million per year spent on infrastructure funding to support breast cancer trials Australian and New Zealand Society of Nephrology See RACP. Jacquot Collaborative Clinical Research Initiative. A new initiative with plans to commit $250,000 a year for 3 years for each project (one new project funded each year). Combines traditional training function with funding for a clinical research project e.g. a trial or epidemiological study.

Collaborative Clinical Trials Group has been initiated for information exchange among nephrologists participating in multi-centre trials.

NHMRC Clinical Research Working Group report 70 Health services / hospitals / universities Organisation Clinical research initiatives Other research training Royal Children’s Hospital, Melbourne 5 Clinical Research Fellowships, registrar pay scales, aimed at clinicians in their last year of advanced training. 50% clinical work and 50% research. 70% of those completing Fellowships go on to take higher research degrees. WA Tissue Bank, administered by WA public and private hospitals and universities Ethics approval obtained at 5 hospitals in Perth, collection not yet started Mental Health and Palliative Care Branch Research Priorities in Mental Health (report – not sighted). Aim is to increase capability for mental health services research (clinical, prevention, health promotion and measurement of outcomes). Prototype identified: Palliative Care with Dr Jack Best Department of Human Services, Victoria State Strategic Health Research Investment Committee established 1999. Clinical research sub-committee to be formed to promote and maintain clinical research in public hospitals and other agencies.

Acute Health Division has responsibility for clinical research within public hospitals, and some funding is provided through the Training and Development Grant as part of casemix funding. The Grant is currently under review, DHS open to opportunities to improve effectiveness and accountability of hospital- based clinical research in Victoria. University of Newcastle, Pathology Established small biotech company to facilitate academic-commercial interaction in research.

NHMRC Clinical Research Working Group report 71 Centre for Family Health and Midwifery, University of Technology, Sydney. Providing Nursing Research Workshops throughout NSW to improve the quality of research applications submitted for Nurses Registration Board scholarships. 70 participants in last 8 months.

NHMRC Clinical Research Working Group report 72 References Note: unpublished sources are acknowledged in the text. Campbell EG, Weissman JS, Moy E, Blumenthal D. Status of clinical research in academic health centres. View from research leadership. JAMA, 2001; 286 (7): 800- 806. Askew DA, Glasziou PP, Del Mar CB. Research output of Australian general practice: a comparison with medicine, surgery and public health. Medical Journal of Australia, 2001; 175: 77-80. Goldbeck-Wood S. Reviving academic medicine in Britain. BMJ, 2000; 320: 591- 592.

Lee S. The crisis in clinical research (letter). JAMA, 1999; 282 (20): 1913. Nathan DG. Clinical research: perceptions, reality, and proposed solutions. JAMA, 1998, 280 (16): 1427-31. NHMRC. Summary of 2000 Grants (as at 15 December 2000). National Health and Medical Research Council Grants Book 2000. Canberra: Australian Government Printing Service, 2000. Rosenberg LE. Physician-scientists – endangered and essential. Science, 1999; 283: 331-2. Schechter AN. The crisis in clinical research. JAMA, 1998; 280 (16): 1440-2. Ward AM, Lopez DG, Kamien M. General practice research in Australia, 1980-1999. Medical Journal of Australia, 2000; 173: 608-611.

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