Around 1,500 cases of oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed in the UK every year . Treatment relies on radiotherapy (RT), surgery with or without post-operative RT or cisplatin-based chemoradiotherapy (CRT), CRT alone or following induction chemotherapy. Increasingly, small molecule adjuvants are also being used. Multi-modality therapy is associated, to varying degrees, with long-term deficits in speech and swallowing function, cosmesis and health-related quality of life.
While the incidence of squamous cancers at most sub-sites of the head and neck is decreasing, the incidence of OPSCC has doubled in the last decade; and this trend is seen throughout the developed world [2, 3]. Oncogenic human papillomavirus type 16 (HPV-16) has been established as the causative agent and has given rise to a clinicopathologically distinct form of OPSCC that occurs in a younger patient population and is associated with improved survival outcomes, compared with HPV-negative disease [4, 5].
Contemporary treatments for HPV-positive and HPV-negative OPSCC are, however, still the same and treatment survivors suffer from long-term sequelae of multi-modality therapy, to varying degrees. Clinical trials in HPV-positive disease are largely focused on deintensifying treatment to improve functional outcomes whilst maintaining the advantageous survival outcomes; however, current research in HPV-negative disease remains focused on improving survival outcomes, with less apparent focus on reducing toxicity and improving functional outcomes. This is largely due to the fact that overall survival rates for HPV-negative disease have remained stubbornly resistant to improvement for many decades.
Despite the fact that available treatments have a significant impact on functioning and quality of life, such outcomes are inconsistently measured and reported between trials. Additionally, there is no standardisation of outcome selection and reporting, even among trials of comparable interventions. This reduces the amount of data contributable for meta-analyses, leading to difficulties in interpreting treatment effect and in making evidence-based healthcare decisions. The development of a minimum outcome reporting standard for OPSCC clinical trials, known as a core outcome set, is one method proposed to address these problems.
A core outcome set defines the outcomes that should be consistently measured and reported in clinical trials in a specific area of health or healthcare. They are developed using consensus methods involving major stakeholders, such as patients and healthcare professionals, to ensure that the outcomes included are clinically relevant and therefore ‘core’.
The existence of a core outcome set does not mean that only these outcomes should be measured; however, if a minimum outcome reporting standard is adhered to, then there will be greater consistency of reporting in clinical trials and a greater body of evidence to contribute to meta-analyses to inform healthcare decisions. Additionally, the risk of outcome reporting bias is lessened by ensuring that outcomes are consistently measured and reported.
The earliest efforts to improve outcome measurement in clinical trials were made by the Outcome Measures in Rheumatology (OMERACT) collaboration in the early 1990s . This international network developed core sets of measures for most of the major rheumatological conditions, and an observational review by Kirkham et al. demonstrated an increase in the consistency of outcome reporting across clinical trials in rheumatoid arthritis (RA) in the years following publication of the RA core outcome set .
The OMERACT collaboration has actively involved patients in discussions about which outcomes to measure in trials since 2002 . Patient involvement was first proposed at the OMERACT meeting in 2000 when participants considered what might be a ‘clinically important change’ in response to treatment. It was realised that the perspectives of patients are important in developing core outcome sets, and they have been actively involved in, and significantly contributed to, all subsequent OMERACT meetings. Patients have enriched the OMERACT research agenda, provided insights into patient participation in research and stimulated patient involvement in health outcomes research more broadly .
Other bodies are now recognising the importance of involving patients in trial research. INVOLVE, the national advisory group for the promotion and advancement of public involvement in NHS, public health and social care research, promotes the involvement of patients and the public in discussions about clinical trials because ‘they are the participants in trials and ultimately the people for whom research is aimed to benefit’ . The Core Outcome Measures in Effectiveness Trials (COMET) Initiative advocates the involvement of patients and the public in decisions about which outcomes should be included in core outcome sets in specific areas of health or healthcare.
The measurement of patient-reported outcomes (PROs) in clinical trials has increased substantially in the last 20 years . These subjective measures help evaluate the burden of disease and treatment from the patient’s perspective. The CONSORT group have recently published a PRO extension to their guidance that aims to improve the reporting of PROs in trials to facilitate the use of results in informing clinical practice and health policy .
Core outcome sets are now in development in a number of clinical areas and their use is advocated, in the UK, by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) and the Cochrane Collaboration [13, 14]. Core outcome sets will only influence the evidence base if they are actually implemented, and as core outcome set developers we must therefore actively engage with trialists, Cochrane Review Groups, clinical guideline developers, research funders, journal editors, regulators and trial registries to act as advocates to ensure that their use is encouraged and supported.
The objective of the CONSENSUS (Squamous Cell CarcinOma of the OropharyNx: Late PhaSE CliNical TrialS; Core OUtcomeS) Study is to develop a core outcome set for OPSCC clinical trials. This protocol presents the methodology to be used.
The first stage of the study will establish the current standard of outcome reporting in clinical trials through a systematic review of OPSCC randomised controlled trials (RCTs). The second stage will involve qualitative interviews with OPSCC patients and carers to establish which outcomes are important to these key stakeholders. The third part of the study will employ an iterative consensus technique known as a Delphi study. We expect that different stakeholder opinions about which outcomes should be measured in clinical trials in OPSCC will converge to achieve consensus on the outcomes in the OPSCC core outcome set.