Eur Spine J. 2014 Apr; 23(4): 772–778.
Published online 2014 Jan 14. doi: 10.1007/s00586-013-3155-0
PMCID: PMC3960418
Institute of Public Health, University of Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Department
of Epidemiology and Biostatistics and the EMGO+ Institute for Health
and Care Research, VU University Medical Center, Amsterdam, The
Netherlands
University College of Health Studies, Campus Kristiania, Oslo, Norway
Warwick Medical School, University of Warwick, Coventry, UK
Department of Health Sciences, Faculty of Earth and Life Science, VU University, Amsterdam, The Netherlands
Nicholas Henschke, Phone: 
+49-6221-565215, Fax: +49-6221-565948, Email: ed.grebledieh-inu@ekhcsneh.
+49-6221-565215, Fax: +49-6221-565948, Email: ed.grebledieh-inu@ekhcsneh.
Corresponding author.
This article has been cited by other articles in PMC.
Abstract
Purpose
To
provide an overview and a critical appraisal of the use of responder
analyses in published randomised controlled trials (RCTs) of
interventions for chronic low back pain (LBP). The methodology used for
the analyses, including the justification, as well as the implications
of responder analyses on the conclusions was explored.
Methods
A
convenience sample of four systematic reviews evaluating 162 RCTs of
interventions for chronic LBP was used to identify individual trials.
Randomised trials were screened by two reviewers and included if they
performed and reported a responder analysis (i.e. the proportion of
participants achieving a pre-defined level of improvement). The cutoff
value for responders, the period of follow-up, and the outcome measure
used were extracted. Information on how RCT authors justified the
methodology of their responder analyses was also appraised.
Results
Twenty-eight
articles (17 %) using 20 different definitions of responders were
included in this appraisal. Justification for the definition of
responders was absent in 80 % of the articles. Pain was the most
frequently used domain for the definition of response (50 %), followed
by back-specific function (30 %) and a combination of pain and function
(20 %). A reduction in pain intensity ≥50 % was the most common
threshold used to define responders (IQR 33–60 %).
Conclusions
Few
RCTs of interventions for chronic LBP report responder analyses. Where
responder analyses are used, the methods are inconsistent. When
performing responder analyses authors are encouraged to follow the
recommended guidelines, using empirically derived cutoffs, and present
results alongside mean differences.
Keywords: Randomised trial, Back pain, Analysis, Responder, Outcomes
Introduction
Chronic
low back pain (LBP) is a common and important cause of functional
disability, work absenteeism and high medical expenses [1].
Many studies have been undertaken to search for effective therapies to
reduce the burden of chronic LBP complaints and its consequences [2].
However, the effectiveness of many interventions for chronic LBP
remains uncertain, as reflected in the findings of numerous randomised
controlled trials (RCTs), systematic reviews and meta-analyses [3].
This uncertainty is often attributed to heterogeneous response to
treatment among patients. A ‘responder analysis’ has been proposed to
offer an additional, clinically meaningful way to facilitate the
interpretation of trial outcomes, especially when treatment response is
heterogeneous [4, 5].
In
the interpretation of clinical trial results, two different aspects of
clinically relevant differences must be distinguished [6].
The first aspect deals with establishing the magnitude of difference in
outcome between the treatment and control groups that is large enough
to define the scientific or therapeutic importance of the results. This
is usually achieved through comparison of summary measures (i.e. mean
differences, when continuous outcome measures are used). The second
aspect deals with determining the proportion of patients who, at an
individual level, achieve a change in the outcome measure which
represents a clinically important change. This can be explored by
analysing the number of individuals who improve beyond a set threshold—a
responder analysis. If, as is often the case, continuous outcomes are
used, the chosen threshold cutoff must be informed by minimally
important change (MIC) for an individual to ‘respond’ to an intervention
as well as the minimal detectable change of the outcome measure in
question [7, 8].
Reporting
of the proportion of participants in a trial who achieve these changes
at specific follow-up time points is suggested to facilitate comparison
of the results of different clinical trials and may help to identify
unique subgroups of patients who respond to certain interventions [6, 9]. Moreover, it allows the calculation of the number needed to treat (NNT) which can further improve interpretation [4].
It is currently unknown to what extent responder analyses are used in
chronic LBP trials and what methodology is used to define a responder to
an intervention. The aim of the current study was to explore the
methodology used to perform responder analyses. The objectives were to
describe the current use of responder analysis in terms of:
justification for the methodology; the outcome measure; the cutoff
values and how they were derived; and the follow-up times at which the
proportion of responders were calculated.