:: Peter Mac :: - Biostatistics and Clinical Trials BaCT

General Information

Publications

Staff

Location

Patient Care

Useful Links

Research

Our Role

To provide high quality, expert statistical and data management support to cancer research undertaken by the Peter MacCallum Cancer Institute (Peter Mac).

Our Mission

To attain the highest standards in the fields of data management and statistics in the design, conduct, analysis and interpretation of cancer clinical and scientific research studies, and to be recognised nationally and internationally for this. We aim to achieve these high standards by keeping up-to-date with international standards and the latest research developments, providing professional standards of collaboration, and contributing to research in our own right.

Overview of the BaCT

Purpose
BaCT provides statistical and data management services for all divisions of Peter Mac. The staff have particular expertise in the design, conduct, analysis and interpretation of cancer clinical trials and retrospective studies, and are experienced in the analysis of other clinical and laboratory research data.

Staff
Our staff of 30 comprise a clinical trials program manager, five statisticians, one IT staff, nineteen data managers, including twelve clinical trial coordinators (trial centre data mangers) and seven study coordinators (local data managers), one administrative BaCT staff and three ALLG Administrative Staff.

Services
BaCT is a leading Australian centre for clinical trials in oncology. We provide randomisation services and trial centre support for multicentre national and international clinical trials, as well as study coordination for trials conducted at Peter Mac. BaCT has expertise in all phases of clinical trials as well as specialist diagnostic trials and treatment planning studies. It is the trial centre for the Australasian Leukaemia and Lymphoma Group (ALLG) and for some trials of the Trans-Tasman Radiation Oncology Group (TROG). BaCT has extensive experience in designing computer databases for both clinical studies and for administrative purposes.

External consultation
As the only major unit of its kind in an Australian hospital, BaCT analyses cancer clinical trials on a contract consulting basis for other hospitals and medical institutions. It also undertakes the analysis of clinical trials and specialised statistical work for national and international institutions and pharmaceutical companies on a negotiated contract basis.

Research
BaCT staff have collaborated on over 200 published papers.

Range of Activities in BaCT (For the year ending in September 2007)

Clinical Trials
BaCT was involved in 119 clinical trials, in 84 of which BaCT was the trial centre (17 phase III, 49 phase II and 18 phase I, pilot or other) and the remaining 35 involved study coordination only. Ninety-three of the 119 trials were multicentre trials. All clinical trials supported by BaCT during this period were investigator-initiated trials.

BaCT is the Trial Centre for the ALLG. During the period there were 19 ALLG trials which were active or undergoing follow-up and which were being coordinated by BaCT, and a further six in development. BaCT was also the Trial Centre for 11 (about half of all) TROG trials, for one Australasian Lung Trials Group and one ANZ Melanoma Trials Group trial. . BaCT also acts as the Australian coordinating centre for a number of trials sponsored by international cooperative cancer trials groups.

Other projects
These included retrospective studies (19), other clinical research (23), and other, including quality assurance studies (19).

Funding of Projects

BaCT receives hospital funding for in-house research projects. All other projects, i.e. those involving non-Peter Mac patients or investigators require external funding (at a Peter Mac cost-neutral rate) to support BaCT’s involvement. This funding is provided by the investigators who enlist BaCT’s support and comes from project-associated grants (e.g. NHMRC and Cancer Councils), Cooperative Group funds, and pharmaceutical companies. (BaCT bases its costings on a detailed database which captures effort-logging activity in terms of hours worked by each staff member on each project.)

History of the BaCT

BaCT had its origins in 1971, when Dr Jane Matthews was appointed as a full-time statistician to the Peter Mac. The Centre underwent a variety of organizational changes. In 1978 the Computer and Bio-Statistical Service (COMPSTAT) was formed, with Dr Ken Koschel as Director and Dr Matthews as Deputy Director. During this time, the data managers involved in clinical research had been part of the Medical Records Department (Health Information Services).

With the growing involvement in clinical research and the close alliance between the statisticians and data managers, these two groups were combined in a separate entity entitled ‘The Statistical Centre’ in 1986, with Dr Matthews as Director. Dr Matthews remained in this position until 2000, when she stepped down to work on a part-time basis. Dr Richard Fisher was appointed the new Director. The Centre changed its name from ‘The Statistical Centre’ to ‘The Centre for Biostatistics and Clinical Trials’ in 2004.

The centre has had a long history of involvement in multi-centre clinical trials, commencing in 1973 when Dr Matthews became the statistician for the newly formed Australian and New Zealand Lymphoma Group (ANZLG). This group later merged with the Australian Leukaemia Study Group (ALSG) to become the ALLG. BaCT is still playing a major role as Trial Centre for the ALLG, together with coordinating many of TROG’s studies.

Since its inception (3 staff in 1971) the number of staff has increased, especially over the last two years.

BaCT Services

BaCT offers the following services:

Design of clinical trials, advice on protocols, sample size and power calculations.

Statistical analysis of data from clinical and scientific studies. Comprehensive written reports with interpretation of the results.

Design of data collection forms for trials, retrospective studies, prospective databases and surveys.

Preparation of randomisation charts and computer-based patient allocation systems. Allocation designs include adaptive biased coin and urn randomisation and dynamic minimization techniques.

Telephone registration and randomisation of patients on clinical trials.

Creation of computer databases for scientific or administrative purposes. Expertise in database software.

Intelligent data entry into databases.

Data collation, checking and clarification with clinicians, nurses and data managers.

Organisation of collaborative group meetings and preparation of newsletters for trial investigators.

Maintenance of collaborative group web sites.

Assistance with preparation of manuscripts, including detailed review of drafts, preparation of graphs, and presentation of manuscripts in a form acceptable to journals.

Advice on methods of statistical analysis and development of new methods if required.

Critical review of manuscripts and publications.

Standards; quality control and security

Laws and regulations of the relevant countries are followed; these include the TGA Notes for Guidance on Good Clinical Practice, the NH&MRC National Statement on Ethical Conduct in Human Research, Medsafe New Zealand Regulatory Guidelines for Medicines and the ICH Guidelines for Good Clinical Practice.

Data entered into computer databases are independently checked using complete visual comparison or double data entry before analysis.

Comprehensive computer data checks are implemented in each database.

Data are rigorously checked by statisticians for consistency and validity prior to analysis.

New statistical software is validated by manual calculation, comparison with computer programs developed by staff or comparison with reliable software.

All statistical reports are checked by the Director or a nominee.

Trial records are securely stored within BaCT which is kept locked whenever staff are absent.

Computers are password protected and are maintained with current virus protection software.

All databases are stored on a central server and backed up by Peter Mac Information Communication Technology (ICT) staff daily.

All records relating to clinical trials are retained for 15 years.

Confidentiality and ethics

All patient records are kept confidential, with access restricted to investigators and trial sponsors for data verification, clarification and reporting purposes.

Confidentiality is maintained for all protocols and trial documentation, with access restricted to the relevant investigators, trial group or sponsoring companies.

All clinical trials require approval from institutional ethics committees.

Business practice

BaCT acts a business unit of Peter Mac. All money earned from external contracts is paid to the Peter Mac, not to individual staff members.

Normally work is done on a fixed price basis with detailed written quotations submitted prior to commencement. Work can be done on an hourly basis if requested.

The Role of a Biostatistician

Design and conduct of clinical trials.
To collaborate with investigators in the design and coordination of clinical studies.
To organise or participate in meetings as required.
To maintain good relations with investigators and other Institute personnel and external clients of BaCT.

Statistical analysis and interpretation of data and report writing.
To analyse and interpret data and write reports on clinical trials and other studies.
To collaborate with investigators in the preparation of manuscripts for publication.
To maintain good relations with investigators and other Institute personnel and external clients of BaCT.

Statistical research
To keep up to date with appropriate statistical methods and relevant literature.
To conduct statistical research into statistical and methodological problems that may arise in clinical trials and to publish the results of that research.

Statistical Education
To provide educational presentations to colleagues as required.

The Role of a Trial Centre Data Manager

Collaboration in trial design.

Collaboration in the development of trial protocols and the review of consent forms.

Design of case record forms.

Preparation of trial operating procedure documents.

Collaboration in the design of trial databases.

Assistance in trial start-up meetings.

Trial conduct

Registration and randomization of patients on trials.

Collection, checking and entering data for in-house and/or multicentre clinical trials in a timely and accurate manner.

Collection of data relating to notification of serious adverse events.

Maintenance of trial databases.

Liaison with data managers and clinicians at participating hospitals.

Compliance with trial protocols.

Quality assurance of collected data - ensure data are timely, complete, accurate and consistent.

Database retrievals as part of quality assurance, analysis, or as requested.

Preparation of newsletters, manuscripts and other publications.

Organization of, and attendance at, meetings of trial groups and deliver presentations if required.

Collaboration in trial analysis

Collaboration with statisticians and investigators in the analysis and reporting of clinical trials.

Quality assurance of data for analysis.

The Role of a Local Data Manager

Cancer clinical trials management
Attend and assist investigator at trial start-up meetings.
Liaise with clinicians and other health professionals to assist in the identification of eligible patients.
Ensure that informed consent has been obtained where appropriate.
Register/randomise all eligible patients according to protocol requirements.
Ensure that appropriate materials (blood samples, slides, X-Rays) are collected and distributed in a secure and timely manner according to protocol requirements.
Organise and/or attend meetings as required.
Identify factors influencing the successful conduct of the clinical trial and take steps to overcome identified problems.

Data collection and completion of case record forms
Ensure that all protocol data collection requirements are met, case record forms are completed accurately and filed or dispatched securely.
Obtain data and complete data collection forms by liaising with clinicians and other health professionals, reviewing patient medical records, using the hospital computer information systems and interviewing patients where appropriate.
Attend outpatient clinics at the PMCI East Melbourne site (and occasionally at time the satellite centres at Moorabbin, Box Hill and Bendigo) to obtain patient data and to set up systems for data collection.
Maintain up-to-date data by developing systems for following up relevant patients in a timely manner.
Maintain integrity of information in the case record forms by identifying missing data, taking steps to collect the data, checking the consistency and accuracy of data and making appropriate corrections.
Send case record forms to coordinating bodies in a timely fashion.
Ensure the relevant authorities are notified of serious adverse events and adverse event forms are completed according to protocol requirements.
Comply with legal, ethical and confidentiality requirements of data collection.

Data entry and database management
Check and enter data for in-house clinical trials in a timely and accurate manner
Maintain trial databases for in-house trials

Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne VIC 3002
Ph: (03) 9656 1111, Fax (03) 9656 1400 (Melway Refrence Map 2G:A2)


	Centre for Biostatistics and Clinical Trials (BaCT) Level 2, No. 10 St Andrew’s Place, East Melbourne

	MAP

	DIRECTION

BaCT data managers are involved in the education of, and obtaining of informed consent from, patients participating in prospective clinical trials at Peter Mac. Data managers are also involved in coordinating patient appointments and assisting patients with the completion of study questionnaires.

Overview of clinical trials

	Clinical trials are experiments in which patients agree to being treated with:

	A new treatment not yet in general use, such as a new chemotherapy drug;

	A known treatment in combination with a new treatment;

	A new supportive care program;

	A survey to document quality of life or patient satisfaction with treatment.

People may benefit from involvement in clinical trials because they may be followed up more rigorously than they would otherwise be, they may receive a better treatment than the currently accepted standard, and they will contribute to the development of better treatments for patients in the future.

Collaborative

Collaborative clinical research is undertaken with investigators within Peter Mac or as part of the Centre's involvement with cooperative Groups, especially the Australasian Leukaemia and Lymphoma Group and the Trans-Tasman Radiation Oncology Group. Staff of the Centre have collaborated in the writing and publication of a number of manuscripts describing the results of analysis of these and other studies. There have been over 200 publications up to 2007.

Biostatistical

The statistical research interests of the Centre include survival analysis and clinical trial methodology. Specific interests include phase II clinical trial designs, rules for monitoring toxicity, stratification in survival studies, design issues in heterogeneous populations, exploratory data analysis, interpretation of negative trials, and competing risks analysis.

Publications by the Centre for Biostatistics and Clinical Trials for the year ending September 2007

Tang, J.I., Williams, S.G., Tai, K.H., Dean, J., Duchesne, G.M. A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy? Brachytherapy 2006 Oct-Dec;5(4):256-261.

Michael, M., Goldstein, D., Clarke, S.J., Milner, A.D., Beale, P., Friedlander, M., Mitchell, P. Prognostic factors predictive of response and survival to a modified FOLFOX regimen: importance of an increased neutrophil count. Clinical Colorectal Cancer 2006 Nov;6(4):297-304.

Philip, J., Gold, M., Milner, A., Di Iulio, J., Miller, B., Spruyt, O. A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer. Journal of Pain and Symptom Management 2006 Dec;32(6):541-550.

Simcock, B., Neesham, D., Quinn, M., Drummond, E., Milner, A., Hicks, R.J. The impact of PET/CT in the management of recurrent ovarian cancer. Gynecologic Oncology 2006 Oct;103(1):271-276.

Antill, Y.C., Reynolds, J., Young, M.A., Kirk, J.A., Tucker, K.M., Bogtstra, T.L., Wong, S.S., Dudding, T.E., Di Iulio, J.L., Phillips, K.A. Screening behavior in women at increased familial risk for breast cancer. Familial Cancer 2006 Nov;5(4):359-368.

Grigg, A.P., Shuttleworth, P., Reynolds, J., Schwarer, A.P., Szer, J., Bradstock, K., Hui, C., Herrmann, R., Ebeling, P.R. Pamidronate reduces bone loss after allogeneic stem cell transplantation. Journal of Clinical Endocrinology and Metabolism 2006 Oct;91(10):3835-3843.

Corry, J., Peters, L., Fisher, R., Macann, A., Jackson, M., McClure, B., Rischin, D. N2-N3 Neck Nodal Control Without Planned Neck Dissection For Clinical/Radiologic Complete Responders—Results Of Trans Tasman Radiation Oncology Group Study 98.02. Head and Neck 2007 (To appear).

Narayan, K., Fisher, R., Bernshaw, D. Patterns of failure and prognostic factor analyses in locally advanced cervical cancer patients staged by MRI and treated with curative intent. Int J Gynecol Cancer 2007 (To appear).

Branford, S., Hughes, T., Milner, A., Koelmeyer, R., Schwarer, A., Arthur, C., Filshie, R., Moreton, S., Lynch, K., Taylor, K. Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-α. Cancer 2007 10:801-808.

Dawson, S.J., Michael, M., Biagi, J., Foo, K.F., Jefford, M., Ngan, S.Y., Leong, T., Hui, A., Milner, A.D., Thomas, R.J., Zalcberg, J.R. A phase I/II trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer. Investigational New Drugs 2007 Apr;25(2):123-129.

Fua, T.F., Corry, J., Milner, A.D., Cramb, J., Walsham, S.F., Peters, L.J. Intensity-modulated radiotherapy for nasopharyngeal carcinoma: Clinical correlation of dose to the pharyngo-esophageal axis and dysphagia. International Journal of Radiation Oncology, Biology, Physics 2007 Mar 15;67(4):976-981.

Lin, M.L., Wirth, A., Chao, M., Milner, A.D., Di Iulio, J., MacManus, M., Seymour, J.F. Radiotherapy for low-grade gastric marginal zone lymphoma: a retrospective study. Internal Medicine Journal 2007 Mar;37(3):172-180.

Mileshkin, L., Honemann, D., Gambell, P., Trivett, M., Hayakawa, Y., Smyth, M., Beshay, V., Ritchie, D., Simmons, P., Milner, A.D., Zeldis, J.B., Prince, H.M. Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines,angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome. Haematologica 2007 Aug;92(8):1075-1082.

Ng, M., Chong, J., Milner, A., MacManus, M., Wheeler, G., Wirth, A., Michael, M., Ganju, V., McKendrick, J., Ball, D. Tolerability of accelerated chest irradiation and impact on survival of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer: review of a single institution's experience. Journal of Thoracic Oncology 2007 Jun;2(6):506-513.

Wong, L.M., Cleeve, L.K., Milner, A.D., Pitman, A.G. Malignant ureteral obstruction: outcomes after intervention. Have things changed? Journal of Urology 2007 Jul;178(1):178-183; discussion 183.

Connell, C.A., Corry, J., Milner, A.D., Hogg, A., Hicks, R.J., Rischin, D., Peters, L.J. Clinical impact of, and prognostic stratification by, F-18 FDG PET/CT in head and neck mucosal squamous cell carcinoma Head and Neck 2007 (To appear).

Grigg, A.P., Gibson, J., Bardy, P.G., Reynolds, J., Shuttleworth, P., Koelmeyer, R.L., Szer, J., Roberts, A.W., To, L.B., Kennedy, G., and Bradstock, K.F.& A prospective multicentre trial of peripheral blood stem cell sibling allografts for acute myeloid leukaemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning. Biology of Blood and Marrow Transplantation 2007 13(5):560-567.

Manoharan, A., Reynolds, J., Matthews, J., Baxter, H., Di Iulio, J., Leahy, M., Juneja, S. Flexible low intensity combination chemotherapy (FLICC) for elderly patients with acute myeloid leukaemia: A multi-centre, phase II study. Drugs and Aging 2007 24(6): 481-488.

Everitt, S.J., Fimmell, N., Reynolds, J., Laferlita, C., Kron, T., Ball, D. and MacManus, M.P. Inter-planner reliability in performing 3DCRT for Non Small Cell Lung Cancer (NSCLC). Australasian Radiology 2007 (To appear).

Mac Manus, M., D'Costa, I., Everitt, S., Andrews, J., Ackerly, T., Binns, D., Lau, E., Ball, D., Weih, L., Hicks, R.J. Comparison of CT and positron emission tomography/CT coregistered images in planning radical radiotherapy in patients with non-small-celll lung cancer. Australasian Radiology 2007 51:386-393.

Everitt, S.J., Schneider-Kolsky, M., Yuen, K., Budd, R., MacManus, M.P. Dose escalation of radical radiation therapy in non-small cell lung cancer (NSCLC) using PET/CT-defined target volumes - are class solutions obsolete? Australasian Radiology 2007 (To appear).

Ryan, G., Martinelli, G., Kuper-Hommel, M., Tsang, R., Pruneri, G., Yuen, K., Roos, D., Lennard, A., Devizzi, L., Crabb, S., Hossfeld, D., Pratt, G., Dell'Olio, M., Choo, S.P., Bociek, R.G., Radford, J., Lade, S., Gianni, A.M., Zucca, E., Cavalli, F., Seymour, J.F. Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group. Annals of Oncology 2007 (To appear). (I.F. 5.179)