The Cochrane Collaboration: Building a global network of systematic reviews in cancer

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Cochrane Cancer Network
Institute of Health Sciences
Headington, Oxford, UK


Abstract

Busy clinicians, policy makers and consumers faced with having to make important decisions about cancer health care need to be able to identify evidence that is relevant, reliable and up-to-date. The Cochrane Collaboration prepares, maintains and promotes the accessibility of systematic reviews of the effects of healthcare interventions. Cochrane reviews are designed to minimise bias and follow a strictly scientific format. Fourteen Cochrane Collaborative review groups are currently preparing and maintaining systematic reviews relating to cancer, covering nearly ninety per cent of cancers. Over 120 Cochrane reviews relating to cancer have been published on The Cochrane Library, now regarded as the best single source of information on the effects of healthcare. A national subscription has been negotiated by the National Institute of Clinical Studies (NICS), enabling all residents of Australia with access to the Internet to have free access to The Cochrane Library. NICS Cochrane Users Awards totalling $11,000 have been established to identify examples of best use. It is important that the needs and perspectives of Australian clinicians and consumers are properly represented in the preparation of Cochrane systematic reviews. Opportunities for clinicians and consumers to become contributors to the Cochrane systematic review process are described.


Introduction

Cancer remains the leading cause of death in Australia with an annual mortality of around 34,700 people. More than 82,000 new cases of cancer are diagnosed each year. One in three men and one in four women can expect to be directly affected by cancer before the age of 751.

Every year tens of millions of dollars are spent worldwide on randomised controlled trials (RCTs) in cancer, investigating the comparative effectiveness of different interventions. But gaining access to the results remains a problem. With over 20,000 biomedical journals being published globally reports of cancer RCTs are easily lost in the flood of information, making it difficult for busy health care professionals to identify the relevant studies, much less make use of the evidence they contain to make daily clinical practice more effective. Despite excellent electronic databases such as Medline and Embase, only a part of the published literature is covered2. The Internet has not proved as helpful as we had hoped in organising the literature; keying in ‘cancer’ on a search engine like Google currently produces over 16 million ‘hits’, often containing unreliable or biased information.

The need for evidence-based care

In order to make well-informed decisions, clinicians, policy makers and consumers need to be able to identify relevant evidence and they need to know whether the evidence underlying the advice they give is valid and up-to-date. This is not news. UK epidemiologist Archie Cochrane drew attention to our great collective ignorance about the effects of health care more than 30 years ago. In his influential book, Effectiveness and efficiency: Random reflections on health services published in 19723, he explained how evidence from RCTs could help us to use resources more rationally. The principles he set out were straightforward: because resources in health care would always be limited, they should be used to provide equitably those forms of health care which had been shown in properly designed evaluations to be effective. Recognising that people who wanted to make more informed decisions about health care did not have ready access to reliable reviews of the available evidence, he argued that priority should be given to finding out which treatments are effective and then ensuring that these treatments are efficiently given to all who need them. In particular, he stressed the importance of using evidence from RCTs because these were likely to provide much more reliable information than other sources of evidence. Writing in 1979, Cochrane commented: “It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomised controlled trials”4.

The Cochrane Collaboration

Archie Cochrane died in 1988 but his encouragement, and the endorsement of his views by others, led to the opening of the first Cochrane Centre (in Oxford, UK) in 1992 and ultimately to the founding of The Cochrane Collaboration in 1993. The Cochrane Collaboration is an international not-for-profit organisation that aims to help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of healthcare interventions. With 81 bases around the world the Cochrane Collaboration operates as a global network and plays a leading role in the international effort to review and synthesise data from intervention studies asking similar questions in health care (using meta-analysis where possible). Cochrane systematic reviews are designed to minimise bias and follow a strictly scientific format. They are published quarterly on The Cochrane Library, and updated at least every two years in order to include the evidence from new trials.

Cochrane reviews are produced by close to 50 Collaborative Review Groups, within which the reviews are prepared and maintained. The members of these Groups – healthcare professionals, researchers, consumers and others – have come together because they share an interest in generating reliable, up-to-date evidence relevant to the prevention, treatment and rehabilitation of particular health problems or groups of problems. Fourteen of these Collaborative Review Groups are responsible for preparing reviews relating to cancer and cover nearly 90 per cent of cancers. Some of these Groups are concerned predominately with cancer (eg the Lung Cancer Review Group based in Barcelona or the Breast Cancer Review Group based in Sydney) while others are concerned with various diseases in an organ system that could include cancer (eg the Hepato-biliary Review Group based in Copenhagen or the Ear, Nose and Throat Disorders Review Group based in Oxford, UK). The scope of Cochrane reviews reflect the clinical need for unbiased information at every stage of the cancer journey. All types of available interventions are reviewed, including: 

  • biological therapy; 
  • chemotherapy; 
  • complementary therapies; 
  • delivery of care; 
  • gene therapy; 
  • hormonal therapy; 
  • immunotherapy; 
  • radiotherapy; 
  • surgery;

and combinations of the above. A list of Cochrane Collaborative Review Groups concerned with cancer is presented in table one. Support is currently being sought for the establishment of a Cochrane Collaborative Review Group in childhood cancer. Reviews in areas where there are no review groups or where the review involves many different types of cancer are overseen by the Gynaecological Cancer Review Group supported by a grant from the UK NHS Research and Development Program.

1565 Cancer Forum July 2003

The work of these Collaborative Review Groups is facilitated and supported by a network of 12 Cochrane Centres spread around the world. They are responsible for coordinating and supporting members of the Collaboration in areas such as training, and for promoting the objectives of the Collaboration at national and regional level. The Australasian Cochrane Centre (www.cochrane.org.au) was established with funding from the Commonwealth Department of Health and Ageing at Flinders University, Adelaide in early 1994 under the directorship of Chris Silagy. In March 1999 the Centre relocated to Monash University, Melbourne. Chris Silagy died on 13 December 2001 after a long battle with non-Hodgkin’s lymphoma. His successor Sally Green continues the Centre’s mission: to train and support reviewers and contributors to the Cochrane Collaboration in Australasia; to conduct research to improve the quality of Cochrane systematic reviews; and to work to inform healthcare decisions through the uptake of Cochrane systematic reviews. Core funding for the Centre comes from the Australian Commonwealth Department of Health and Ageing.

Cochrane systematic reviews

In 1987 Cynthia Mulrow revealed the poor state of the contemporary medical review article showing it to be all too often subjective, scientifically unsound and inefficient. She proposed criteria by which trials might be systematically reviewed5. Ten years later Viv Bramwell and Chris Williams showed that there had been little improvement in the field of cancer. Using Mulrow’s criteria, they evaluated the methodological quality of review articles including meta-analyses published over a 12-year period in a major cancer journal. They found that, with the exception of the meta-analyses, the majority of authors had not used systematic methods to identify, assess and synthesise information6.

There are currently over 1,500 Cochrane systematic reviews published on The Cochrane Library7. Prepared by experienced health care professionals and peer reviewed at both the protocol stage and at pre-publication, these independent, high-quality reviews are presented in a systematic, unbiased way and are updated regularly to include evidence from the latest trials. Readers are provided with the opportunity to offer their comments or criticisms online, thereby improving the quality of the systematic reviews. Over 120 of these reviews relate to cancer. Although this represents a good starting point, more needs to be done to encourage the production of systematic reviews in cancer, particularly relating to more common cancers. Authors of good quality non-Cochrane reviews and meta-analyses are being approached by the Cochrane Cancer Network and invited to turn their papers into Cochrane reviews. Based at the Institute of Health Sciences in Oxford, UK, the Cochrane Cancer Network (Director: Chris Williams) is developing a list of high priority questions (‘hot topics’) for systematic review or new trials in cancer. Following discussions with the UK’s National Cancer Research Network it has issued an international standing invitation to individuals (clinicians, cancer nurses, patients and researchers) and organisations (cancer charities, funding bodies and support groups, research institutes) to suggest five questions that they would most like to see addressed in a Cochrane systematic review. Its current list of ‘hot topics’ covers a broad spectrum of cancer care interventions including: 

  • cancer prevention; 
  • screening for cancer; 
  • treatment; 
  • the control of treatment side effects; 
  • rehabilitation; 
  • palliative care; 
  • symptom control; 
  • psychosocial effect of cancer; and 
  • organisation of cancer care.

One critical area of cancer care – diagnosis – has so far been omitted from the Cochrane canon due to the methodological difficulties such reviews present. At its meeting in Melbourne earlier this year the Cochrane Collaboration Steering Group agreed to take forward a program of work to extend the definition of Cochrane systematic reviews to include systematic reviews of diagnostic test accuracy. Clearly, this will not happen overnight. There is much work to be done before systematic reviews of diagnostic test accuracy can be included in The Cochrane Library, but success in this area promises tremendous benefits to both cancer health care professionals and their patients.

Building an evidence-based research agenda

As Cochrane emphasised, reviews of research evidence must not only be prepared systematically, they must be kept up-to-date in order to take account of new evidence. If systematic reviews are not properly maintained, important effects of health care (good and bad) will not be identified promptly, and people using the health services will be ill-served as a result. In addition, without systematic, up-to-date reviews of previous research, plans for new research cannot be well informed. Researchers and funding bodies may miss promising leads or embark on studies asking questions that have already been answered8. It is this capacity to prevent duplication of effort and place proposed or completed trials within the context of existing research that is leading to the systematic review’s gradual replacement of the RCT at the top of the hierarchy of evidence when determining the comparative effectiveness of health care interventions. As Mulrow observed in 1994: “The hundreds of hours spent conducting a scientific study ultimately contribute only a piece of an enormous puzzle. The value of any single study is derived from how it fits with and expands previous work, as well as from the study’s intrinsic properties. Through systematic review the puzzle’s intricacies may be disentangled”9.

Supporting the preparation and maintenance of systematic reviews, even at its current level, represents a phenomenal effort by the Cochrane Collaboration’s 8,000 contributors. Identifying as many relevant studies as possible is a prerequisite for preparing high quality systematic reviews. Of its 81 bases located around the world, 54 either are conducting, or have conducted, manual searches of journals publishing reports of controlled trials relating to cancer. The Cochrane Cancer Network maintains an overview of these searches. By February 2003, 334 journals were either being or had been retrospectively searched and 201 were being prospectively searched, representing approximately 5,600 years of journal publication. From a baseline of around 8,000 reports identified on Medline in 1996 (when the Cochrane Cancer Network was established), the number of trials identified by the Cochrane Collaboration had grown to over 26,000 by February 2003. 

Dissemination

The Cochrane Collaboration provides and promotes access to its systematic reviews through The Cochrane Library. Updated quarterly and distributed on an annual subscription basis on disk, CD-ROM and via the Internet The Cochrane Library is the main output of the Cochrane Collaboration and is now regarded as the best single source of information on the effects of health care. It currently includes the following databases:

The Cochrane Database of Systematic Reviews containing systematic reviews and protocols of upcoming systematic reviews of healthcare interventions, prepared and maintained by Collaborative Review Groups.

The Database of Abstracts of Reviews of Effects assembled and maintained by the NHS Centre for Reviews and Dissemination in York, England, containing critical assessments and structured abstracts of other systematic reviews, conforming to explicit quality criteria.

The Cochrane Central Register of Controlled Trials (CENTRAL) containing bibliographic information on hundreds of thousands of controlled trials, including reports published in conference proceedings and many other sources not currently listed in other bibliographic databases.

The Cochrane Database of Methodology Reviews containing Cochrane methodology reviews and protocols of methodological studies prepared by the Methodology Review Group.

The Cochrane Methodology Register containing references to articles and books on the science of reviewing research. The Cochrane Library also contains a Handbook on how to conduct a systematic review, and a glossary of terms.

The Cochrane Collaboration section in The Cochrane Library contains contact details and other information about Collaborative Review Groups and the other contributing entities within the Cochrane Collaboration.

In October 2002 Australia obtained a national subscription to The Cochrane Librarynegotiated by the National Institute of Clinical Studies (NICS) on behalf of the Commonwealth Government of Australia. This subscription enables all residents of Australia with access to the Internet to have free access to The Cochrane Library. The NICS Cochrane Users Award was launched at the same time, designed to recognise and reward the best use of research evidence contained in The Cochrane Library for enhancing patient care. A total of $11,000 will be awarded to seven individuals, or groups, who can demonstrate excellent use of The Cochrane Library to improve clinical care. The winning entry will receive $5,000; five runners-up will receive $1,000 each and an additional award of $1,000 will also be made for improvements in maternal and perinatal health. Applicants for all awards categories must submit a publication-ready, 500-word abstract explaining how evidence they found in The Cochrane Library contributed to the improvement of health care for Australians.

The Cochrane Library will eventually be joined by a new Cochrane product designed especially for the cancer community. The Cochrane Cancer Network is currently discussing with John Wiley & Sons (who have recently taken on the role of publishing The Cochrane Library) the publication of The Cochrane Library: a specialised database of evidence-based information relating to cancer including both Cochrane and non-Cochrane systematic reviews as well as a maintained register of controlled trials in cancer.

Good decisions about health care

Reliable evidence about the effects of specific interventions in cancer is only part of what is needed for good decisions about health care. The results of Cochrane reviews should be integrated with the dual expertise of the clinician (which has been acquired through experience and practice) and of the patient (which derives from their knowledge of their condition, the treatments on offer and their preferences, and the likelihood of success and treatment side-effects). Similar qualifications are appropriate when considering the relevance of Cochrane reviews in decisions taken in respect of whole communities. Local disease burdens and barriers to implementation vary widely from country to country and from place to place within countries. Local attention to these issues will help to ensure that the evidence will help those who can best benefit from it. It is important that the needs and perspectives of Australian clinicians and consumers are properly represented in the preparation of Cochrane systematic reviews.

Existing opportunities for contribution

A number of opportunities exist for clinicians and consumers to become contributors to the Cochrane systematic review process:

  • as a reviewer or by collaborating with other health professionals, consumers or researchers on a Cochrane systematic review; 
  • as a consumer, offering valuable insights to reviews; 
  • as a peer-reviewer of protocols and reviews relating to cancer prior to their publication on The Cochrane Library
  • as an advisor on methodological issues; 
  • as a volunteer, helping to search for the evidence by hand-searching journals, conference proceedings etc, particularly in languages other than English; and 
  • as a funder, providing financial support to the review process. 

The Cochrane Cancer Network provides a useful liaison point for cancer health care specialists around the world interested in contributing to the work of the Collaboration. It supplies information about the progress of Cochrane reviews in cancer and offers a forum for networking among cancer Collaborative Review Groups within the Collaboration. The Australasian Cochrane Centre holds regular training workshops designed to meet the needs of both new and more experienced reviewers.

Conclusion

Daily, clinicians and others confront questions about the effectiveness of preventive and therapeutic interventions in cancer, the interpretation of diagnostic tests, the harm associated with exposure to a particular agent, the course of disease and the cost-effectiveness of what they do. Health professionals and their patients need to be able to make sense of all the research going on around the world. Healthcare decision-making throughout the world will be informed by high quality, timely research evidence. The Cochrane Collaboration is playing a pivotal role in the production and dissemination of this evidence across all areas of cancer.

Acknowledgements

The author would like to thank Chris Williams, Sally Green and Kate Stevens for their kind help with this paper.

References

1. The Cancer Council Australia. “Facts and figures: Cancer in Australia”. The Cancer Council Australia, www.cancer.org.au, 2003.

2. S Hopewell, M Clarke, C Lefebvre, R Scherer. “Handsearching versus electronic searching to identify reports of randomized trials (Cochrane Methodology Review)”. In: The Cochrane Library, Issue 2, Update Software, Oxford, 2003.

3. AL Cochrane. Effectiveness and Efficiency. Random Reflections on Health Services. Nuffield Provincial Hospitals Trust, London, 1972.

4. AL Cochrane. “1931-1971: a critical review, with particular reference to the medical profession.” In: Medicines for the year 2000, Office of Health Economics, London, 1979, pp1-11.

5. CD Mulrow. “The medical review article: state of the science.” Ann Int Med, 106 (1987): 485-8.

6. VH Bramwell, CJ Williams. “Do authors of review articles use systematic methods to identify, assess and synthesize information?” Ann Oncol, 8, 12 (1997): 1185-95.

7. The Cochrane Library, Issue 2, Update Software, Oxford, 2003.

8. EM Antman, J Lau, B Kupelnick, F Mosteller, TC Chalmers. “A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts.” JAMA, 268 (1992): 240-8.

9. CD Mulrow. “Systematic Reviews: Rationale for systematic reviews.” BMJ, 309 (1994): 597-9.

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