Pain relief that matters to patients: systematic review of empirical studies assessing the minimum clinically important difference in acute pain

Jørgen Hilden,Asbjørn Hróbjartsson,Britta Tendal,Maria Damkjær Hansen,Eik Bjerre,Mette Frahm Olsen,Nino Emanuel Landler

doi:10.1186/s12916-016-0775-3

Abstract

BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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.

Highlights

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
This interpretation problem for clinical relevance has been at the core of debates of the importance of several types of interventions intended for reducing acute pain, for example, paracetamol [1,2,3], non-steroidal anti-inflammatory drugs [4, 5], morphine or synthetic opiates [6], corticosteroids [7], muscle relaxants [4], laser therapy [8], transcranial direct current stimulation [9], EMLA cream [10], and acupuncture [11]
Eligibility criteria We included prospective studies of patients with acute pain, regardless of age, clinical condition, and intervention, in which pain intensity was assessed on a onedimensional scale, e.g. a 100 mm visual analogue scale (VAS) or a 0–10 point numerical rating scale (NRS), and in which the MCID was determined using an anchorbased method using patients’ perception of change to determine clinical importance

Summary

Introduction

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. The degree of pain reduction that is considered clinically relevant has an impact on which analgesic interventions are regarded clinically useful This interpretation problem for clinical relevance has been at the core of debates of the importance of several types of interventions intended for reducing acute pain, for example, paracetamol [1,2,3], non-steroidal anti-inflammatory drugs [4, 5], morphine or synthetic opiates [6], corticosteroids [7], muscle relaxants [4], laser therapy [8], transcranial direct current stimulation [9], EMLA cream [10], and acupuncture [11]. The strength of the concept is that it defines a relevant effect size based on clinical considerations and statistical significance [13, 14] It has subsequently been supplemented by a related concept – the substantial (and minimum) clinically relevant difference [15]

Methods

Results

Discussion

Conclusion