title: Comparative effectiveness of chemopreventive interventions for colorectal cancer: protocol for a systematic review and network meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with substantial socioeconomic burden. Despite considerable research, including numerous randomised controlled trials (RCTs) and systematic reviews assessed the effect of various chemopreventive interventions for CRC, there remains uncertainty regarding the comparative effectiveness of these agents. No network meta-analytic study has been published to evaluate the efficacies of these agents for CRC. Therefore, the aim of this study is to summarise the direct and indirect evidence for these interventions to prevent CRC in average-high risk individuals, and to rank these agents for practical consideration.
  
  
  METHODS
  We will acquire eligible studies through a systematic search of MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, CINAHL plus, IPA and clinicaltrials.gov website. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are the incidence of CRC, the incidence/recurrence of any adenoma or change in polyp burden (number or size). Quantitative synthesis or meta-analysis will be considered. We will also construct a network meta-analysis (NMA) to improve precision of the comparisons among chemo-preventive interventions by combining direct and indirect evidence. The probability of each treatment being the best and/or safest, the number-needed-to-treat [NNT; 95% credible interval (CrIs)], and the number-needed-to-harm (NNH; 95% CrIs) will be calculated to provide measures of treatment efficacy. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA.
  
  
  RESULTS
  This protocol has been registered (registration number: CRD42015025849) with the PROSPERO (International Prospective Register of Systematic Reviews). The procedures of this systematic review and NMA will be conducted in accordance with the PRISMA-compliant guideline. The results of this systematic review and NMA will be submitted to a peer-reviewed journal for publication.
  
  
  CONCLUSIONS
  To the best of our knowledge, this study will be the first NMA to identify the comparative effectiveness of interventions for the prevention of CRC. The results of our study will update evidence for chemoprevention of CRC, identify key areas for future research, and provide a framework for conducting large systematic reviews involving indirect comparisons.
authors: School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia ;
authors: Sajesh K
authors: SK
authors: Veettil
authors: School of Pharmacy, Monash University, Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia;; Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao Muang, Phayao 56000, Thailand;; Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand;
authors: Surasak
authors: S
authors: Saokaew
authors: Clinical School, Department of Surgery, International Medical University, Jalan Rasah, Seremban, 70300, Negeri Sembilan, Malaysia ;
authors: Kean Ghee
authors: KG
authors: Lim
authors: Department of Family Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Malaysia;; Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia;
authors: Siew Mooi
authors: SM
authors: Ching
authors: Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand ;
authors: Pochamana
authors: P
authors: Phisalprapa
authors: School of Pharmacy, Monash University, Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia;; Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand;; School of Population Health, University of Queensland, Brisbane, Australia;; School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
authors: Nathorn
authors: N
authors: Chaiyakunapruk
keywords: Protocol; chemoprevention; colorectal neoplasms; network meta-analysis (NMA); randomised controlled trials (RCTs); systematic review