Details of HTA project in progress
Last updated: 21 May 2013 - Next update due: 28 May 2013
Research type: |
Primary Research (e.g. trial) |
Project title: |
The ROMIO trial. Randomised Oesophagectomy: Minimally Invasive or Open, a feasibility study |
 Outputs in journals arising from this project
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Project ref: |
10/50/65 |
Cost: |
£408,062 |
Chief Investigator : |
Dr Chris Metcalfe, Reader in Medical Statistics & MB ChB prog Yr4 Lea, School of Social and Community Medicine, University of Bristol |
Start Date: |
January 2013 |
Estimated date of publication in HTA journal series: |
Early 2016. This date takes account of time for report preparation and printing based on current average times for these activities. |
Plain English Summary |
Oesophageal cancer (cancer of the gullet) is becoming increasingly common in the UK. If it is detected early, it may be cured with surgery (oesophagectomy) alone or combined with chemotherapy. Traditionally this was performed with large incisions in the abdomen, the chest and sometimes the neck, to remove the cancer and replace the gullet with the stomach. The operation is complex, is associated with complications in up to 60% of patients, and about one in 20 patients die in-hospital shortly after the surgery. Surgery initially significantly reduces quality of life, and recovery may take 12 months. The benefit of surgery is survival and about 40% of patients live for 3 post operative years. Given the nature of this surgery, and the chances of long term survival, it is important that patients recover swiftly from surgery and regain quality of life. Recent developments with minimally invasive ‘keyhole’ surgery for oesophageal cancer suggest that this approach may achieve the same survival benefit, but with better recovery than open surgery. However, no randomized trials have been undertaken and the apparent faster recovery may be due to the selection of fitter patients for the less familiar and technically challenging minimally invasive procedures. Conducting randomized trials in surgery is recognised as being difficult as, for example, patients need to be assured that there is no better informed method than random allocation for deciding their treatment, and surgical techniques may continue to change which makes evaluation complex. Consequently, before we proceed with a definitive trial comparing open and minimally invasive techniques for oesophagectomy, we are proposing a preliminary study to refine the research methods and to assess the feasibility of the main trial. This preliminary work, based around a small scale pilot of the main randomised trial, will establish processes to inform patients about the trial in a balanced way (with the aim of improving recruitment whilst avoiding unintentional coercion), blind patients and assessors to their treatment allocation, define the exact surgical techniques for the main trial, test trial procedures, define the important outcomes and establish the main costs involved in each of the interventions. We will develop methods of measuring surgical skill with the different procedures, which will be used in the main trial to ensure involved surgical teams are achieving acceptable standards. By dedicating time to this preliminary work, we can allow a full contribution from our patient representative as we develop our plans and procedures for the main trial, in addition to which we will formally assess the acceptability of study procedures to pilot trial participants. Products of the preliminary study will be an indication of the feasibility of the main trial (e.g. if more than half of the eligible patients agree to take part in the pilot trial, at least once recruitment procedures have been refined in the latter stages); a detailed main trial protocol (which we will aim to publish with relevant supporting data from the preliminary study) and grant application for the main trial, and methodological papers in peer-reviewed journals describing that methodological work which can be applied to other surgical trials. No ethical issues are anticipated beyond the need to ensure patients are fully informed about the study before they decide whether to take part. A key aspect of the preparatory work proposed here is a formal investigation of the appropriate way to present this information to potential participants. The open and minimally invasive procedures are already undertaken in participating centres, so the treatments themselves pose no risks beyond those associated with routine clinical care. The preliminary study and anticipated main trial will be managed by a close collaboration between clinicians at two specialized surgical centres (Bristol and Plymouth), and academic experts in research methodology at the University of Bristol. Bristol and Plymouth are leading clinical centres in the use of minimally invasive procedures for oesophagectomy. At the School for Social and Community Medicine, University of Bristol, there is extensive experience in running large and challenging trials in the NHS (e.g. the ProtecT trial of treatments for localised prostate cancer, the CAP trial of UK population level PSA testing to reduce prostate cancer mortality). The school hosts the Bristol Randomised Trials Collaboration (UKCRC/NCRI-accredited) and the MRC ConDuCT Hub for trials methodology research. In the 2008 Research Assessment Exercise, 80% of Health Services Research conducted at the school was rated 3* or 4* (world leading or internationally excellent). Resources are requested to employ a researcher at the University of Bristol to co-ordinate the feasibility study, develop the core outcome sets, analyse the qualitative data and establish a surgical competency assessment tool. A second researcher working half-time for one year at Imperial College will develop a standardized method of processing the pathological specimens, and contribute to the development of measures of treatment fidelity. A researcher in health economics, employed for three months at the University of Bristol, will work on establishing the main cost and methods of measuring them. We have a research nurse at the Bristol clinical centre, and plan to employ a second nurse at the Plymouth clinical centre to recruit participants, co-ordinate the qualitative data collection and follow up patients. One part time secretary will type qualitative interviews and provide administrative support for the trial. In addition we are requesting funds for equipment (computers, audio recorders, video cameras); and a limited number of face to face meetings (travel and subsistence for management and scientific meetings) which will be arranged to coincide where appropriate and will be supplemented by telephone conferencing to reduce the costs and environmental impact of the study. |
Project Abstract: |
DESIGN: This feasibility study is built around a pilot two-centre pragmatic randomised controlled trial comparing minimally invasive and open surgical procedures in the treatment of oesophageal cancer. The feasibility work includes qualitative analysis to identify hurdles to recruitment; evaluation of methods for blinding of patients and outcome assessors; and the development of a core outcome measure set. We anticipate that the key obstacles to progression to the main trial are strong surgeon and patient preferences. These issues will impact on recruitment of patients to the study, and will be addressed by the integrated qualitative research. If it proves impossible to randomise more than 50% of eligible patients even towards the end of the pilot RCT, then an informative main trial may well not be feasible. SETTING: Two centres, University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust. Both centres have teams of upper gastro intestinal cancer surgeons (6 in Bristol and 5 in Plymouth). TARGET POPULATION: Over a 12-month period (starting in 2012) consecutive referrals of patients with oesophageal cancer for oesophagectomy at the Bristol and Plymouth centres. HEALTH TECHNOLOGIES BEING ASSESSED: In the pilot trial we will compare 2-phase open oesophagectomy; 2-phase laparoscopically assisted oesophagectomy; and Totally minimally invasive oesophagectomy . This comparison of procedures in the pilot trial will be crucial in informing the procedures to be compared in the main trial. MEASUREMENT OF OUTCOMES: The key outcomes from the pilot trial, which will inform the decision of whether to proceed with the main trial are counts of the number of potentially eligible patients per month per centre, the proportion of these patients confirmed as eligible, the proportion of patients agreeing to be randomly allocated to a study procedure in the pilot RCT, and the proportion of randomised patients completing outcome measurements. The primary and secondary outcome measures for the main trial will be determined during the feasibility study based upon expert input from the study steering committee and the consensus meetings held to inform the core outcome set. Currently the primary outcome for the main trial is planned to be a patient report of fatigue using the MFI20. Participants will be asked to complete measurements at baseline, and on the second day (assessments of pain and blinding only), 6 days, 6 weeks, 3 months and 6 months after surgery. MEASUREMENT OF COSTS: The best way of capturing resource use (e.g. questionnaires, logs, electronic versus hard copy medical records) and cost in relation to the interventions and follow-up in secondary care will be explored. SAMPLE SIZE: At the two lead centres, recruitment to the pilot RCT will occur over a 12-month period, with 72 potentially eligible patients being expected during that time. This will allow a true 50% recruitment rate to be estimated with a 95% confidence interval of approximately 38% to 62%. PROJECT TIMETABLE: Prior to the start of the study will seek to obtain ethical approval, establish governance procedures, agree contracts, and recruit study staff. We propose to run the feasibility study for two years, with pilot trial recruitment starting at three months, continuing for twelve months, and follow-up completed six months after that. We anticipate recruiting six patients per month; 72 over the 12 month recruitment period. Study milestones include the successful start and completion of the pilot trial recruitment in months 3 and 15, the successful completion of the pilot trial follow-up in month 21, and the protocol plus funding application for the main trial at the close of this feasibility study. |
Project Protocol: |
Project protocol (pdf format, 309 kbytes) |
URL of this page: |
http://www.hta.ac.uk/2827 |
Outputs from this project
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