title: Pain relief that matters to patients: systematic review of empirical studies assessing the minimum clinically important difference in acute pain.
abstract: BACKGROUND
  The minimum clinically important difference (MCID) is used to interpret the clinical relevance of results reported by trials and meta-analyses as well as to plan sample sizes in new studies. However, there is a lack of consensus about the size of MCID in acute pain, which is a core symptom affecting patients across many clinical conditions.
  
  
  METHODS
  We identified and systematically reviewed empirical studies of MCID in acute pain. We searched PubMed, EMBASE and Cochrane Library, and included prospective studies determining MCID using a patient-reported anchor and a one-dimensional pain scale (e.g. 100 mm visual analogue scale). We summarised results and explored reasons for heterogeneity applying meta-regression, subgroup analyses and individual patient data meta-analyses.
  
  
  RESULTS
  We included 37 studies (8479 patients). Thirty-five studies used a mean change approach, i.e. MCID was assessed as the mean difference in pain score among patients who reported a minimum degree of improvement, while seven studies used a threshold approach, i.e. MCID was assessed as the threshold in pain reduction associated with the best accuracy (sensitivity and specificity) for identifying improved patients. Meta-analyses found considerable heterogeneity between studies (absolute MCID: I2= 93%, relative MCID: I2= 75%) and results were therefore presented qualitatively, while analyses focused on exploring reasons for heterogeneity. The reported absolute MCID values ranged widely from 8 to 40 mm (standardised to a 100 mm scale) and the relative MCID values from 13% to 85%. From analyses of individual patient data (seven studies, 918 patients), we found baseline pain strongly associated with absolute, but not relative, MCID as patients with higher baseline pain needed larger pain reduction to perceive relief. Subgroup analyses showed that the definition of improved patients (one or several categories improvement or meaningful change) and the design of studies (single or multiple measurements) also influenced MCID values.
  
  
  CONCLUSIONS
  The MCID in acute pain varied greatly between studies and was influenced by baseline pain, definitions of improved patients and study design. MCID is context-specific and potentially misguiding if determined, applied or interpreted inappropriately. Explicit and conscientious reflections on the choice of a reference value are required when using MCID to classify research results as clinically important or trivial.
authors.affiliation: Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, Department 7811, 2100, Copenhagen Ø, Denmark.
authors.forename: Mette Frahm
authors.identifier: http://orcid.org/0000-0002-5742-6403
authors.initials: MF
authors.lastname: Olsen
authors.affiliation: University Hospitals' Centre for Health Research (UCSF), Rigshospitalet, Blegdamsvej 9, Department 9701, 2100, Copenhagen Ø, Denmark.
authors.forename: Eik
authors.initials: E
authors.lastname: Bjerre
authors.affiliation: Frederiksberg Hospital, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark.
authors.forename: Maria Damkjær
authors.initials: MD
authors.lastname: Hansen
authors.affiliation: Section of Biostatistics, University of Copenhagen, Østre Farigmagsgade 5, 114, Copenhagen Ø, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Hilden
authors.affiliation: Department of Cardiology, Herlev-Gentofte Hospital, Kildegårdsvej 28, 2900, Hellerup, Denmark.
authors.forename: Nino Emanuel
authors.initials: NE
authors.lastname: Landler
authors.affiliation: Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, Department 7811, 2100, Copenhagen Ø, Denmark.
authors.forename: Britta
authors.initials: B
authors.lastname: Tendal
authors.affiliation: Centre for Evidence-Based Medicine, University of Southern Denmark & Odense University Hospital, Sdr. Boulevard 29, Gate 50 (Videncenteret), 5000, Odense C, Denmark. Asbjorn.Hrobjartsson@rsyd.dk.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Hróbjartsson
mesh_terms: D059787:Acute Pain / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004185:Disability Evaluation; D006801:Humans; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D055815:Young Adult
keywords: Minimum clinically important difference; Pain; Systematic review