Randomised Controlled Trials of Interventions to Prevent Oral Mucositis in Patients UndergoingTreatment for Cancer

  • Gemma Bryan

Student thesis: Phd


IntroductionOral mucositis is an inflammatory and frequently ulcerative side effect of cancertherapy, which has been identified by patients as the most debilitating side effect oftheir treatment. Mucositis is a dose limiting toxicity which exerts a substantial clinicaland economic impact and negatively affects patient quality of life. The patientexperience of mucositis is under-reported in the literature. To date, no interventionshave been identified that have proven successful in the prevention of mucositis forpatients receiving all types of therapy. Vitamin E has shown conflicting results inclinical trials. This thesis combines appraisal of the literature and empirical research,and uses lessons learned from previous studies together with the results of a feasibilitystudy to identify a best practice model for future trials.MethodsThe Cochrane risk of bias (ROB) instrument was used to assess the ROB in the studiesincluded in the Cochrane prevention review. A sensitivity analysis was conducted afterstudies assessed at unclear or high risk of overall bias were excluded. A systematicreview of assessment instruments was conducted which identified 50 instruments.Consideration of the appropriateness of these instruments for the use in a clinical trialfor the prevention of mucositis was based on the practicality, comparability, andreproducibility, and the impact of these instruments on patients. Three of theseinstruments were chosen for use in a clinical trial of adults undergoing stem celltransplant. Finally, a feasibility study was designed, developed and conducted whichinvestigated vitamin E for the prevention of mucositis in patients undergoingconditioning for bone marrow transplantation. Through lessons learned from previousstudies, consultations with medical professional, the MHRA, ethics committee andsuppliers, a protocol was developed for a double blind RCT. The process of gainingMHRA and ethical approval, and the repackaging of intervention and placebo productsto meet MA-IMP requirements are described.Results130 articles were assessed for risk of bias. Only ten studies were assessed as being atlow overall risk of bias. Blinding of outcome assessors and adequate allocationconcealment were identified to be important considerations in the planning of futurestudies. Although only nine patients were recruited into the feasibility study, a numberof issues affecting the design and conduct of future trials were identified. Recruitment inparticular was identified to be problematic. Strategies for overcoming this problem infuture trials were discussed. The methods of blinding and allocation concealmentemployed were found to be feasible for use in future trials. Expected adverse eventspatients undergoing stem cell transplantation were also reported.ConclusionFurther studies are required to investigate interventions for the prevention of mucositis.It is of upmost importance that these trials are rigorous in both their methodology andsubsequent reporting in order to elicit the maximum benefit for patients taking part inclinical trials, and future patients undergoing therapy for cancer.
Date of Award1 Aug 2011
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorAlexander Molassiotis (Supervisor)


  • Vitamin E
  • Risk of Bias
  • Oral Assessment
  • Feasibility Study
  • Randomised Controlled Trial
  • Oral Mucositis
  • Systematic Review

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