title: Identifying placebo responders and predictors of response in osteoarthritis: a protocol for individual patient data meta-analysis.
abstract: The management of osteoarthritis (OA) is unsatisfactory, as most treatments are not clinically effective over placebo and most drugs have considerable side effects. On average, 75 % of the analgesic effect from OA treatments in clinical trials can be attributed to a placebo response, and this response varies greatly from patient to patient. This individual patient data (IPD) meta-analysis aims to identify placebo responders and the potential determinants of the placebo response in OA.
  
  
  
  This study is undertaken in conjunction with the OA Trial Bank, an ongoing international consortium aiming to collect IPD from randomised controlled trials (RCTs) for all treatments of OA. RCTs for each treatment of OA have been systematically searched for, and authors of the relevant trials have been contacted to request the IPD. We will use the IPD of placebo-controlled RCTs held by the OA Trial Bank for this project. The IPD in placebo groups will be used to investigate the placebo response according to the minimum clinically important difference (MCID) threshold (e.g. 20 % pain reduction). Responders to placebo will be compared with non-responders to identify predictors of response. The quality of the trials will be assessed and potential determinants will be examined using multilevel logistic regression analyses.
  
  
  
  This study explores the varying magnitude of the placebo response and the proportion of participants that experience a clinically important placebo effect in OA RCTs. Potential determinants of the placebo response will also be investigated. These determinants may be useful for future studies as it may allow participants to be stratified into groups based on their likely response to placebo. The results of this study may also be useful for pharmaceutical companies, who could improve the design of their studies in order to separate the specific treatment from the non-specific contextual (i.e. placebo) effects.
  
  
  
  PROSPERO CRD42016033212.
authors: School of Healthcare, University of Leeds, Leeds, UK.
authors: Yu
authors: Y
authors: Fu
authors: Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK.|Arthritis Research UK Pain Centre, Nottingham, UK.
authors: Monica S M
authors: MS
authors: Persson
authors: Arthritis Research UK Centre for Sports, Exercise and Osteoarthritis, Nottingham, UK.|Academic Orthopaedics, Trauma and Sports Medicine, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Archan
authors: A
authors: Bhattacharya
authors: Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK.|Arthritis Research UK Centre for Sports, Exercise and Osteoarthritis, Nottingham, UK.|Sports Medicine Unit, University of Malaya, Kuala Lumpur, Malaysia.
authors: Siew-Li
authors: SL
authors: Goh
authors: Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK.|Arthritis Research UK Pain Centre, Nottingham, UK.
authors: Joanne
authors: J
authors: Stocks
authors: Department of General Practice, Erasmus MC Medical University, Rotterdam, The Netherlands.
authors: Marienke
authors: M
authors: van Middelkoop
authors: Department of General Practice, Erasmus MC Medical University, Rotterdam, The Netherlands.
authors: Sita M A
authors: SM
authors: Bierma-Zeinstra
authors: Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK.|Arthritis Research UK Pain Centre, Nottingham, UK.
authors: David
authors: D
authors: Walsh
authors: Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK.|Arthritis Research UK Pain Centre, Nottingham, UK.
authors: Michael
authors: M
authors: Doherty
authors: Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, NG5 1PB, UK. weiya.zhang@nottingham.ac.uk.|Arthritis Research UK Pain Centre, Nottingham, UK. weiya.zhang@nottingham.ac.uk.
authors: Weiya
authors: W
authors: Zhang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D006801:Humans; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal
keywords: Individual patient data meta-analysis; Osteoarthritis; Placebo response