Identifying and prioritising gaps in colorectal cancer trials research in Australia

In 2011, we reported a mismatch between the burden of disease and the number of clinical trials in various types of cancer.1 For example, colorectal cancer had the highest incidence (14 234 cases) and the second highest mortality (4047 deaths) of all cancers in 2007,2 but only the sixth largest number of cancer trials.1 Similarly, poor correlation between burden of disease and public funding of trials has been reported.3,4 These mismatches are not limited to cancer. In osteoarthritis, consumers placed a higher priority on research to evaluate knee replacement, education and physical therapy, but 60% of the studies undertaken evaluated drugs or injections.5 Such mismatches may result in evidence “gaps” where the information needed to inform clinical treatment decisions is unavailable.5 Further, even when appropriate trials have been conducted, areas of uncertainty or controversy may remain, again contributing to evidence “gaps”.

The aims of our study are (i) to identify evidence gaps in the treatment and prevention of colorectal cancer from the perspective of consumers, health professionals, researchers and funding bodies; (ii) to identify trials that could be undertaken to fill those evidence gaps; and (iii) to prioritise clinical trials that could be undertaken by Australian research groups. As part of (iii), we explored the barriers to conducting trials and opportunities to facilitate clinical trials in Australia.

In this study, we focused on colorectal cancer trials and included the perspectives of consumers, health professionals, researchers and funding bodies. We also provided a comprehensive view of priorities for colorectal cancer trials research, allowing differences in perspectives to be examined.

The study was conducted jointly by the University of Sydney and the Australasian Gastro-Intestinal Trials Group (AGITG), which is Australia’s largest independent non-profit organisation conducting clinical trials in the area of gastrointestinal cancers.6 The study consisted of two components: a review of colorectal cancer trial activity; and consensus meeting discussions informed by the review.

Until recently, there was little research about the extent to which the trial questions addressed by researchers matched questions that were important to clinicians and patients.10 However, significant progress has been made in this area since 2004 with the establishment of the James Lind Alliance, a not-for-profit independent organisation in the United Kingdom that aims to identify and prioritise research questions of importance to both patients and clinicians.11 Through “Priority Setting Partnerships” they have established a set of guidelines that include quantitative and qualitative methods (including holding focus groups) to incorporate the views of interested groups.12 The aim of Priority Setting Partnerships is to produce a “top ten” list of research questions that have the potential to be used by research groups and the pharmaceutical industry.13-16

Despite progress in this area, the optimal way to identify and prioritise relevant research is unknown. It is likely that involving research and funding groups from the outset is important. Using clinical trial registry data and obtaining the background research at the start of the process may be a more efficient way to prioritise research questions. Rather than broad research questions, specific clinical trial questions may be more useful for research groups.

To avoid publication bias, we used clinical trial registry data to summarise trial activity in colorectal cancer. Despite efforts to increase the rates of registration of clinical trials, registration is not compulsory in Australia, so the results may be incomplete. It is possible that because our search strategy included “colorectal” or “bowel” and “cancer”, we may have missed some trials in the area of prevention or those related to the quality of colonoscopy.

The main priority areas identified by O’Dwyer et al included the importance of prevention and screening trials to reduce the burden of colorectal cancer, and the role of individualised treatments.7 They did not compare the views of different groups on priority areas for research.

In our study, we used similar categories to O’Dwyer et al so that we could assess the progress made in colorectal cancer trials research since 1 January 2005. A strength of our study is that we explored the views of different groups, recognising that those with an interest in colorectal cancer bring a range of perspectives on priority questions. As reported previously, it is important that research agenda encompass consumer views, so that research findings are relevant to consumer needs.5 We made an effort to source consumers with a range of experience and knowledge, although the final group of participants comprised people affected by colorectal cancer. This may have influenced perspectives about screening in the general population. Participating researchers included a pathologist involved in laboratory research, a public health researcher, a psychologist involved in quality-of-life research, four medical oncologists, and a radiation oncologist and a surgeon who were involved as principal investigators of clinical trials. It is likely that the outcomes of our study were influenced by the composition of the final group of participants, although the broad representation means that it is likely that the results are generalisable to people with an interest in colorectal cancer research in other countries. Consumers, health professionals and researchers were asked to identify specific trial questions. Although they found this challenging, participants felt that it was more useful to discuss ideas for specific trials that could be developed by research groups, rather than a list of general research areas.

We found a potential mismatch between areas in which trials are being conducted and those prioritised by consumers, health professionals and researchers. The review of trial registry data showed that most trials recruiting patients in Australia and worldwide are testing a range of drugs for use in advanced disease. In contrast, all groups emphasised the need for research in the areas of risk and prevention, screening and survivorship care. A number of specific trials were proposed to fill these gaps. Examples include primary prevention of colorectal cancer with aspirin, and two strategies to increase screening uptake — one in those at above-average risk, and one in healthy adults aged 50 years and over. This is pertinent in the context of the federal government’s recent announcement to expand the National Bowel Cancer Screening Program to include people aged 60 years from 2013 and people aged 70 years from 2015. All groups discussed the development of individualised therapies (treatments that are often tested initially in the setting of advanced disease). Other common areas of need that were identified included diagnosis, quality of life and survivorship care (particularly, evaluating the long-term effects of treatment on quality of life and new ways to follow up people affected by colorectal cancer), and health services research.

There were differences among the topics for future research identified by consumers, health professionals and researchers. For example, the researchers discussed investigating new targeted therapies (eg, stem cells) and understanding mechanisms of resistance to existing treatments in advanced disease, while the consumers discussed whether earlier diagnosis and treatment of metastatic disease would affect outcomes, and how patient expectations can be managed in the setting of advanced disease. Consumers also identified further questions about palliative care, including comparing the experience of dying at home rather in the hospice, and the burden of home death on relatives.

Prevention and screening trials are more difficult to conduct than treatment trials because of the large numbers of patients that need to be recruited, and the high level of funding required. As identified during the consensus meeting, there are opportunities for collaborative research between the AGITG and the Primary Care Collaborative Cancer Clinical Trials Group. The importance of undertaking this research is supported by health economic data, which could help to attract the funding required. The research effort in advanced disease needs to continue, with the goal of individualising patient care to achieve the best outcomes. Routine biobanking will be critical for this to be achieved. The findings from this study could potentially be used by the AGITG and other interested research groups to develop clinical trial protocols.