Title: Development of a core outcome set for informed consent, clinical trials and treatment policy in patients with anal cancer
Funder: Department of Health and Social Care

Abstract: Background: Anal cancer was once thought to be an uncommon malignancy occurring in elderly individuals &ndash; but in the past 20 years, its clinical presentation has changed considerably. Treatment of anal cancer is complex: initial treatment is chemo-radiotherapy, but local relapse occurs in approximately 20% - cases in which radical salvage surgery is considered. Overall, these treatments are associated with considerable short and long-term morbidities. There have been several trials and studies of interventions in patients with anal cancer, and these underpin current clinical practice. However, for each of these studies, several different endpoints have been reported. Lack of standardisation in reporting makes it very difficult to truly discuss likely outcomes of treatment with patients in the clinic i.e. informed consent. This proposal is about the development of a core outcome set. The selection of appropriate outcomes or domains is crucial for clinical decision-making and designing clinical trials, in turn, benefitting patients. The COMET (core outcome measures in effectiveness trials) initiative is a guidance for developing and reporting core outcome measures through integrating patient relevant outcomes within sets. Aims: The overall aim is to develop a core outcome set for the treatment of anal cancer which reflects the interests of patients, clinicians, commissioners, and trialists in order to facilitate decision-making by all stakeholders. Research questions: There are four research questions &ndash; corresponding to the four work packages in the plan of investigation: What are the outcomes reported in trials and studies assessing the effectiveness of interventions for anal cancer &ndash; both as primary/initial treatment and after salvage therapy? What are the outcomes patients with anal cancer regard as potentially important following treatment? From (1) and (2), what are the most important outcomes for each key stakeholder group? Can we derive a core outcome set from the three sets of key outcomes from the stakeholder groups? Research team: Investigators from Manchester, Liverpool, and other national experts, aligned with national initiatives. Plan of investigation: A clinical research fellow will be recruited and register as a 2 year MD thesis. The project will be undertaken within a COMET framework and have four work packages. WP1: A systematic review of literature on anal cancer interventions will be performed. We will focus on two broad areas - (i) primary treatment and (ii) after local relapse &ndash; salvage therapy - and identify a comprehensive list of clinical, patient-reported, healthcare 'process', resource, composite and surrogate outcomes reported in anal cancer treatment studies. WP2: Semi-structured interviews with anal cancer survivors will be used to identify additional outcomes. WP3: Surveys of key stakeholders (patients, clinicians, commissioners) in three rounds of Delphi methodology will refine the outcome long-list into a core outcome set. WP4: Consensus meetings with key stakeholders will ratify the core outcome set. Potential impact: There is no published core outcome set for anal cancer. This research will standardise core outcome definition, collection, measurement, analysis and interpretation in this field. It will benefit all stakeholders i.e. patients, clinicians and health care providers in the UK and beyond. The impact of the proposed project is best appreciated in the context of important parallel national developments and recent changes in the NHS England structure &ndash; namely: (i) The development of an Association of Coloproctology of Great Britain and Ireland supported national anal cancer audit database (lead: Renehan) (ii) The development of a national ACTIII (Anal Cancer) trial in anal cancer to start in 2016 (leads: Sebag-Montefiore, Adams); and (iii) The Clinical Commissioning Group Outcomes Indicator Set. The results of this project will feed directly into all three of these.

Lay abstract: Over the past three decades, anal cancer has become more common (1000 new cases in England per year) and presents in younger patients. Treatment is complex, and includes radiotherapy and chemotherapy, and surgery in up to a quarter of cases. The UK has led the world in large-scale national trials in the treatment of anal cancer. Until now, these trials have improved the cure of anal cancer, but at a price &ndash; namely, high rates of short and long-term complications. We are developing a new generation of clinical practice and trials, focusing on maintaining high cure rates, but minimising adverse effects and without loss of quality of life for patients. To-date, studies have reported their results &ndash; outcomes &ndash; as tumour control and survival. There is now a need to develop a wider but core set of outcomes that are relevant for patients &ndash; known as patient-related outcomes. Investigators from Manchester, Liverpool, and other national experts, aligned with national initiatives, propose to develop these outcomes within a framework known as COMET (core outcome measures in effectiveness trials). We will use a stepwise systematic research plan through four work packages &ndash; a comprehensive literature review; a semi-structured series of interviews with anal cancer survivors to identify outcomes to include in the core set; then, three rounds of a method known as Delphi methodology to refine the outcome long-list into a core outcome set; and finally a consensus meetings with key stakeholders to ratify the final set. At the end of 2 years, we will have established, what outcomes are most relevant for patients, and how and when to measure these. This will benefit patients through better informed consent on current treatment and will improve patient information as part of recruitment into future trials.

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CANCER AND NEOPLASMS