Abstract
Background:
Identifying changes in pain score associated with clinically meaningful outcomes is necessary when using self-report measures to assess pain in children. We aimed to determine the changes in pain score associated with a minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient-perceived adequate analgesia (PPAA), and to evaluate for differences based on initial pain intensity and patient characteristics.
Methods:
Cross-sectional study of children 6-17 and 4-17 years old who were assessed using the Verbal Numerical Rating Scale (VNRS) and Faces Pain Scale-Revised (FPS-R), respectively. Children qualitatively described any endorsed change in pain score; those who received an analgesic were asked if they wanted additional analgesics to decrease their pain intensity. We used a receiver operating characteristic curve-based methodology to identify changes in pain score associated with “a little less” and “much less” pain (MCSD and ICSD, respectively) and patients declining additional analgesics because of adequate analgesia (PPAA).
Results:
We enrolled 431 children with painful conditions. For the VNRS, raw change and percent reductions in pain scores associated with MCSD, ICSD, and PPAA were 2/10 and 20%, 3/10 and 44%, and 2/10 and 29%, respectively; for the FPS-R, 2/10 and 33%, 4/10 and 60%, and 4/10 and 40%, respectively. Raw change in pain scores increased with increasing initial pain intensity, but percent reductions remained stable. There were no significant differences based on patient characteristics such as age, sex, and race/ethnicity.
Conclusion:
Our findings provide patient-centered outcomes in children that are suitable for designing trials and are generalizable across patient characteristics.
INTRODUCTION
Pain scales such as the Verbal Numerical Rating Scale (VNRS) and Faces Pain Scale – Revised (FPS-R) are frequently used to assess changes in pain intensity in children with painful conditions. These self-report measures of pain have strong validity and reliability in children with acute pain. 1,2 In order to properly use these measures to assess pain in children, it is necessary to identify changes in pain score associated with clinically meaningful outcomes. These changes in pain score can be used by researchers to design trials based on outcomes and effect sizes that are clinically meaningful to patients, and may be one way for clinicians to determine whether their treatment had a clinically meaningful effect on their patients.1–4
Previously reported clinically meaningful outcomes include the minimum clinically significant difference (MCSD) and ideal clinically significant difference (ICSD), which typically represent a change in pain score that a child reports to be “a little less” and “much less”, respectively. 5–7 However, these outcomes have not been consistently defined across different self-report measures in children presenting with acute pain, which is necessary prior to their implementation in practice. The generalizability of any clinically meaningful outcome also needs to be evaluated across patients with different initial pain intensities and differing characteristics. A decrease in pain score considered to be meaningful has been shown to vary based on a patient’s initial pain intensity, and a child’s age, sex, and race/ethnicity are related to their ability to describe and quantify pain, as well as their perception of and sensitivity to pain. 5,8–15
In addition, a limitation of the MCSD and ICSD is that they do not explicitly address a clinically important goal for children with pain -- namely, whether the child feels that his/her pain has been adequately treated. We define the clinically meaningful outcome of “patient-perceived adequate analgesia” (PPAA) as the change in pain score associated with a child declining additional analgesia to make his/her pain intensity less after an initial treatment is administered because he/she feels that his/her pain has been adequately treated. The change in pain score representing PPAA is an outcome measure and has not been previously described, and may be a more patient-centered outcome than the MCSD and ICSD. It is unknown if changes in pain score representing an MCSD or ICSD are the same as the change in pain score representing PPAA.
We aimed to determine the changes in pain score in children with acute pain associated with the MCSD, ICSD, and PPAA, when using the VNRS and FPS-R. Our secondary aim was to determine and compare the MCSDs, ICSDs, and PPAAs based on initial pain intensity and patient characteristics such as age group, sex, and race/ethnicity. Our exploratory aim was to determine and compare these clinically meaningful outcomes based on primary language and etiology of pain.
METHODS
Study Design
We conducted an observational cross-sectional study. The institutional review board approved this study with verbal informed consent.
Study Setting and Population
We conducted this study in an urban pediatric emergency department (ED) with an annual census of approximately 55,000 visits. This study was part of a larger pain scale validation study that included children with both painful and non-painful conditions.1 This planned secondary analysis only included children with painful conditions. We enrolled a convenience sample of children aged 4 to 17 years with painful conditions as identified by the triage nurse and confirmed by the study team by asking children themselves whether they had “any pain” or “any hurt”. Children who responded affirmatively were considered to have a painful condition. We excluded children if they had developmental delay or neurologic impairment, intoxication, altered mental status, a medical condition necessitating multiple painful procedures (e.g. malignancy), a chronic disease associated with pain (e.g. sickle cell disease), or if they did not speak English or Spanish.
Measurements
The VNRS has demonstrated strong convergent validity, known-groups validity, responsivity, and test-retest reliability in children 6- to 17-years-old with acute pain.1 The VNRS was administered by asking, “On a scale from zero to ten, where zero means no pain and ten means the most or worst pain, how much pain do you have right now?” The interaction was verbal, using no materials or equipment. The FPS-R (Figure 1) has demonstrated strong convergent validity, known-groups validity, responsivity, and test-retest reliability in children 4- to 17-years-old with acute pain.2 The FPS-R was administered by showing the child a picture of the pain scale, and reading standardized instructions in English or Spanish (www.iasp-pain.org/FPSR). For both the VNRS and FPS-R, the word “hurt” was used interchangeably with “pain”, depending on what seemed most understandable for each child. Children were documented as not understanding the VNRS if they did not respond, responded with a nonnumeric response, or a number outside of the 0 to 10 range, when asked twice. Children were considered as not understanding the FPS-R if they did not respond or select a face when asked twice.
Figure 1.
The Faces Pain Scale – Revised. Each face represents an increasing degree of pain, moving from left to right, scored 0, 2, 4, 6, 8, 10. Note. From: “The Faces Pain Scale – Revised: Toward a common metric in pediatric pain measurement” by Hicks CL, von Baeyer CL, Spafford PA et al. Pain. 93,173–183. Copyright 2001 by International Association for the Study of Pain®. Reprinted with permission. http://www.iasp-pain.org/FPSR.
Procedures
We performed two serial assessments of pain intensity in each child’s primary language. Children were not provided with the pain intensity score reported during the first assessment when the second assessment was performed. For both the first and second assessments, the child was asked to report his/her pain intensity first on the VNRS, and then on the FPS-R. An analgesic was administered at the treating physician’s discretion after the first assessment. If the child had received an analgesic, the second assessment was conducted 30-60 minutes after analgesic administration. During the second assessment, the child was asked: “Is your pain much less, a little less, about the same, a little worse, or much worse compared to before you got your medicine?” The child was then asked, “Do you want more medicine to make your pain less?” The word “hurt” was used interchangeably with “pain”, and the word “smaller” was used interchangeably with “less”, depending on what seemed most understandable for each child. If the child responded that he/she did not want more medicine, he/she was asked for the reason why. If the child stated it was because his/her pain was adequately relieved, then his/her response was documented as “no” (i.e. not wanting more medicine to make his/her pain less). If the child declined medicine for reasons unrelated to pain relief (e.g. medication tasted bad, did not want a needle, afraid of side effects), the study team member would attempt to address and alleviate these concerns and then revisit the child’s desire for additional analgesia. Specifically, the study team member would ask if the child would want any additional medicine to make his/her pain less if there was an analgesic available that did not have any of the specifically disclosed issues, or any other anticipated negative effects. This was repeated until all endorsed concerns were addressed. If the child still declined after having addressed all endorsed concerns, his/her response was documented as “no” (i.e. not wanting more medicine to make his/her pain less). This interaction was conducted in such a way as to elicit the preferences of the child rather than the caregiver present with the child.
If the child did not receive an analgesic, the second assessment was conducted 30-60 minutes after the first assessment was performed. During the second assessment, the child was asked, “Is your pain much less, a little less, about the same, a little worse, or much worse compared to how you felt about [number of minutes since last assessment] ago?” or “…compared with how you felt the last time I asked you how much pain or hurt you had?” depending on what was most understandable for each child. Children who did not receive an analgesic were not asked if they wanted additional analgesia to make their pain less.
Outcome Measures
The minimum clinically significant difference (MCSD) and ideal clinically significant difference (ICSD) are the changes in pain score associated with a child reporting that his/her pain intensity is “a little less” or “much less”, respectively. 5–7 Patient-perceived adequate analgesia (PPAA) is an outcome measure developed by the authors and described here for the first time. We defined PPAA as the change in pain score associated with a child declining additional analgesia to make his/her pain intensity less after an initial treatment is administered because he/she feels that his/her pain has been adequately treated (as opposed to declining additional analgesia for other reasons such as fear of side effects). A child was determined to have experienced PPAA if they responded “no” when asked, “Do you want more medicine to make your pain less?” using the specified procedure described above. Patient-perceived adequate analgesia is conceptually similar to the previously-described “Perceived Need for Medicine”, which is the pain score at which a child answers “yes” to questions such as, “Do you feel the need for more pain medicine right now?” or the pain score which a child reports when asked what pain score would be the minimum to warrant treatment. 15,16 However, PPAA is a change in pain score while Perceived Need for Medicine is a single pain score.
Data Analyses
Descriptive statistics were used to describe the characteristics of patients enrolled, and the changes in pain scores endorsed by children who reported a MCSD, ICSD, and PPAA. For the VNRS, children aged 6- to 17-years-old were analyzed. For the FPS-R, children aged 4- to 17-years-old were analyzed. For both pain scales, patients were removed if they did not provide a response consistent with the valid options available for each scale (e.g. for the FPS-R, selecting the space in between two faces, instead of selecting a face itself). For the MCSD and ICSD determination, patients were removed from analysis if they did not understand, or did not respond to, the question asked at the second assessment to qualitatively describe their change in pain. For the PPAA determination (which is relevant only to patients who have received an analgesic), patients were removed from analysis if 1) they did not receive an analgesic, or 2) they did not understand, or did not respond to, the questions asked regarding whether they wanted additional analgesia.
To determine the change in pain score with the best test characteristics associated with MCSD, ICSD, and PPAA, we used a method based on the receiver operating characteristic (ROC) curve. ROC-based methods use dichotomous reference criteria to determine cut points for continuous measures that optimally differentiate between the two classes of the criteria. 5,17,18 Specifically, we determined the sensitivity, specificity, and area under the curve (AUC) of all possible cut points and determined the cut point as optimal that had the lowest absolute difference between sensitivity and specificity (and therefore the highest AUC). We used three different reference criteria: First, for MCSD we compared children who reported that their pain was “a little less” or “much less” to those whose pain was “about the same”, “a little worse”, or “much worse”. Second, for ICSD we compared children who reported that their pain was “much less,” to those whose pain was “a little less”, “about the same”, “a little worse”, or “much worse”. Third, for PPAA we compared children who answered “no” when asked if they wanted additional analgesia to make their pain less (which represented patient-perceived adequate analgesia) to those who answered “yes” to the same question. To guard against finding spurious differences, we used bootstrapping to determine the magnitude of the variability of each cut point.19 We reported the change in pain score for the MCSD, ICSD, and PPAA as both a raw change and a percent reduction in pain score.
To evaluate for differences in MCSD, ICSD, and PPAA based on initial pain intensity, we determined each within categories of initial pain intensity (i.e. mild, moderate, and severe) for both pain scales using the same ROC-based methods described earlier. We defined the categories of initial pain intensity using conventionally accepted thresholds (i.e. 1-3 = mild, 4-6 = moderate, and 7-10 = severe).20–22 Similarly, to evaluate for differences based on patient characteristics, we determined and compared the MCSD, ICSD, and PPAA for subgroups based on age group (younger, 6 to 7 years for VNRS and 4 to 7 years for FPS-R; older, 8 to 17 years); sex (female and male); race/ethnicity (Hispanic, Black, and White); primary language (English and Spanish); and etiology of pain (traumatic and non-traumatic). The age categories were selected to stratify younger patients into age groups that have been shown to demonstrate more variability in their accuracy and responses when describing pain . 23,24
The sample size was based on the parent study for which this study was a planned secondary analysis.1 We conducted statistical analyses using SPSS (version 24; IBM Corporation, Armonk, NY) and R (version 3.5; R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
Characteristics of Study Subjects
From April 2014 to March 2016, we enrolled 431 children with painful conditions (Figure 2), with Table 1 showing the characteristics of the patients analyzed for each clinically meaningful outcome when using the VNRS and FPS-R. There were more patients reporting an initial pain score representing severe pain intensity (i.e. 7-10) when using the VNRS compared to the FPS-R, with the understanding that the VNRS has more pain score options to choose from that represent severe pain intensity (i.e. 7, 8, 9, or 10 for the VNRS, compared to 8 or 10 for the FPS-R).
Figure 2.
Patient enrollment.
Table 1:
Patient characteristics
| Analyzed for VNRS | Analyzed for FPS-R | |||
|---|---|---|---|---|
| Characteristic | MCSD/ICSD | PPAA | MCSD/ICSD | PPAA |
| n=342 | n=239 | n=413 | n=275 | |
| n (%) | n (%) | n (%) | n (%) | |
| Sex | ||||
| Female | 172 (50.3) | 121 (50.6) | 200 (48.4) | 134 (48.7) |
| Male | 170 (49.7) | 118 (49.4) | 213 (51.6) | 141 (51.3) |
| Age, years | ||||
| 4 | N/A | N/A | 42 (10.2) | 24 (8.7) |
| 5 | N/A | N/A | 45 (10.9) | 27 (9.8) |
| 6 | 46 (13.5) | 25 (10.5) | 45 (10.9) | 25 (9.1) |
| 7 | 47 (13.7) | 19 (7.9) | 47 (11.4) | 19 (6.9) |
| 8 | 17 (5) | 10 (4.2) | 17 (4.1) | 10 (3.6) |
| 9 | 27 (7.9) | 17 (7.1) | 26 (6.3) | 16 (5.8) |
| 10 | 18 (5.3) | 14 (5.9) | 17 (4.1) | 13 (4.7) |
| 11 | 30 (8.8) | 25 (10.5) | 27 (6.5) | 22 (8) |
| 12 | 29 (8.5) | 24 (10) | 29 (7) | 24 (8.7) |
| 13 | 24 (7) | 21 (8.8) | 21 (5.1) | 18 (6.5) |
| 14 | 33 (9.6) | 28 (11.7) | 29 (7) | 24 (8.7) |
| 15 | 29 (8.5) | 25 (10.5) | 28 (6.8) | 24 (8.7) |
| 16 | 24 (7) | 20 (8.4) | 23 (5.6) | 19 (6.9) |
| 17 | 18 (5.3) | 11 (4.6) | 17 (4.1) | 10 (3.6) |
| Race/ethnicity | ||||
| Hispanic | 271 (79.2) | 188 (78.7) | 325 (78.7) | 217 (78.9) |
| Black | 44 (12.9) | 32 (13.4) | 57 (13.8) | 36 (13.1) |
| White | 19 (5.6) | 13 (5.4) | 23 (5.6) | 16 (5.8) |
| Other1 | 8 (2.3) | 6 (2.5) | 8 (1.9) | 6 (2.2) |
| Primary language | ||||
| English | 312 (91.2) | 225 (94.1) | 376 (91) | 255 (92.7) |
| Spanish | 30 (8.8) | 14 (5.9) | 37 (9) | 20 (7.3) |
| Painful condition | ||||
| Soft tissue injury | 93 (27.2) | 79 (33.1) | 107 (25.9) | 83 (30.2) |
| Abdominal pain | 79 (23.1) | 48 (20.1) | 88 (21.3) | 54 (19.6) |
| Headache | 42 (12.3) | 34 (14.2) | 45 (10.9) | 35 (12.7) |
| Ear/throat pain | 41 (12) | 24 (10) | 58 (14) | 36 (13.1) |
| Fracture | 20 (5.8) | 17 (7.1) | 23 (5.6) | 20 (7.3) |
| Back pain | 14 (4.1) | 8 (3.3) | 15 (3.6) | 8 (2.9) |
| Chest pain | 12 (3.5) | 8 (3.3) | 12 (2.9) | 8 (2.9) |
| Abscess | 12 (3.5) | 10 (4.2) | 10 (2.4) | 7 (2.5) |
| Laceration | 1 (0.3) | 0 | 9 (2.2) | 7 (2.5) |
| Other | 28 (8.2) | 11 (4.6) | 46 (11.2) | 17 (6.2) |
| Initial pain score reported | ||||
| 0 | 4 (1.2) | 3 (1.3) | 22 (5.3) | 9 (3.3) |
| 1-3 | 45 (13.2) | 14 (5.8) | 87 (21.1) | 38 (13.8) |
| 4-6 | 112 (32.7) | 71 (29.7) | 180 (43.6) | 129 (46.9) |
| 7-10 | 181 (52.9) | 151 (63.2) | 124 (30) | 99 (36) |
| Reported change in pain | ||||
| Much less | 73 (21.3) | 57 (23.8) | 95 (23) | 74 (26.9) |
| A little less | 146 (42.7) | 124 (51.9) | 164 (39.7) | 132 (48) |
| About the same | 87 (25.4) | 44 (18.4) | 106 (25.7) | 49 (17.8) |
| A little more | 23 (6.7) | 7 (2.9) | 26 (6.3) | 7 (2.5) |
| Much more | 13 (3.8) | 7 (2.9) | 22 (5.3) | 13 (4.7) |
| Analgesics administered | ||||
| Ibuprofen | 124 (36.3) | 124 (51.9) | 144 (34.9) | 144 (52.4) |
| Parenteral opioid | 53 (15.5) | 53 (22.2) | 57 (13.8) | 57 (20.7) |
| Acetaminophen | 38 (11.1) | 38 (15.9) | 48 (11.6) | 48 (17.4) |
| Ketorolac | 13 (3.8) | 13 (5.4) | 11 (2.7) | 11 (4) |
| Oral opioid-containing analgesia | 4 (1.2) | 4 (1.7) | 3 (0.7) | 3 (1.1) |
| Other2 | 7 (2) | 7 (2.9) | 12 (2.9) | 12 (4.4) |
| No analgesic administered | 103 (30.1) | N/A | 138 (33.4) | N/A |
Other = American Indian or Alaska Native, Asian, more than one, and “Don’t know”
Includes both pharmacological and non-pharmacological (e.g. ice packs) analgesics
VNRS = Verbal Numerical Rating Scale. FPS-R = Faces Pain Scale – Revised. MCSD = Minimum clinically significant difference. ICSD = Ideal clinically significant difference. PPAA = Patient-perceived adequate analgesia.
Main Results
Tables 2 and 3 show the minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient-perceived adequate analgesia (PPAA) as raw change and percent reduction in pain score and the associated test characteristics for the VNRS and FPS-R, respectively. The raw change in pain score representing PPAA was similar to the MCSD when using the VNRS, and similar to the ICSD when using the FPS-R. The percent reduction changes in pain score representing PPAA for both pain scales were greater than the MCSD and less than the ICSD. Supplemental Tables 1 and 2 show, for both the VNRS and FPS-R, a trend of increasing raw change score associated with increasing initial pain intensity for MCSD, ICSD, and PPAA, respectively. The percent reduction in pain score remained similar across all three categories of initial pain intensity for the VNRS, but only across categories of moderate and severe initial pain intensity for the FPS-R. For both pain scales, raw change and percent reduction in scores associated with MCSD, ICSD, and PPAA appeared to be similar between subgroups based on age, sex, race/ethnicity, primary language, or etiology of pain (Supplemental Tables 3 and 4).
Table 2:
Changes in VNRS pain scores representing MSCD, ICSD, and PPAA and associated test characteristics
| Change in pain score (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | AUC (95% CI) | |
|---|---|---|---|---|
| MCSD1 | ||||
| Raw change score | 2 (1, 2) | 0.74 (0.69, 0.92) | 0.89 (0.71, 0.93) | 0.88 (0.84, 0.91) |
| Percent reduction | 20 (14, 22) | 0.82 (0.75, 0.86) | 0.81 (0.76, 0.86) | 0.84 (0.79, 0.89) |
| ICSD2 | ||||
| Raw change score | 3 (3, 3) | 0.74 (0.63, 0.84) | 0.78 (0.73, 0.83) | 0.83 (0.76, 0.88) |
| Percent reduction | 44 (40, 50) | 0.77 (0.72, 0.85) | 0.80 (0.74, 0.83) | 0.82 (0.77, 0.87) |
| PPAA3 | ||||
| Raw change score | 2 (2, 3) | 0.74 (0.53, 0.80) | 0.59 (0.52, 0.78) | 0.70 (0.63, 0.77) |
| Percent reduction | 29 (25, 33) | 0.69 (0.61, 0.74) | 0.67 (0.62, 0.74) | 0.72 (0.66, 0.78) |
VNRS = Verbal Numerical Rating Scale. AUC = Area under curve. MCSD = Minimum clinically significant difference. ICSD = Ideal clinically significant difference. PPAA = Patient-perceived adequate analgesia. Sensitivity, specificity, and AUC reflect the ability of the determined change in pain score to identify those who have or have not experienced a specific clinically meaningful outcome (i.e. MCSD, ICSD, or PPAA).
Number of patients endorsing MCSD=146
Number of patients endorsing ICSD=73
Number of patients endorsing PPAA=136
Table 3:
Changes in FPS-R pain scores representing MSCD, ICSD, and PPAA and associated test characteristics
| Change in pain score (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | AUC (95% CI) | |
|---|---|---|---|---|
| MCSD1 | ||||
| Raw change score | 2 (2, 2) | 0.85 (0.81, 0.89) | 0.79 (0.73, 0.86) | 0.86 (0.82, 0.90) |
| Percent reduction | 33 (25, 33) | 0.81 (0.77, 0.88) | 0.82 (0.75, 0.86) | 0.85 (0.80, 0.90) |
| ICSD2 | ||||
| Raw change score | 4 (4, 4) | 0.63 (0.53, 0.73) | 0.79 (0.74, 0.83) | 0.78 (0.74, 0.83) |
| Percent reduction | 60 (60, 67) | 0.80 (0.71, 0.84) | 0.77 (0.74, 0.82) | 0.79 (0.75, 0.84) |
| PPAA3 | ||||
| Raw change score | 4 (2, 4) | 0.51 (0.44, 0.84) | 0.78 (0.49, 0.84) | 0.71 (0.65, 0.76) |
| Percent reduction | 40 (40, 50) | 0.71 (0.63, 0.76) | 0.70 (0.65, 0.78) | 0.74 (0.68, 0.79) |
FPS-R = Faces Pain Scale – Revised. AUC = Area under curve. MCSD = Minimum clinically significant difference. ICSD = Ideal clinically significant difference. PPAA = Patient-perceived adequate analgesia.
Sensitivity, specificity, and AUC reflect the ability of the determined change in pain score to identify those who have or have not experienced a specific clinically meaningful outcome (i.e. MCSD, ICSD, or PPAA).
Number of patients endorsing MCSD=164
Number of patients endorsing ICSD=95
Number of patients endorsing PPAA=157
Figure 3 shows the distribution of pain scores reported that were associated with a MCSD, ICSD, and PPAA for the VNRS and FPS-R. A large proportion of children endorsed a change in pain score that was greater than the changes in pain score representing MCSD, ICSD, and PPAA that we identified in this study (Tables 2 and 3). For the VNRS, 51 (34.9%), 45 (61.6%), and 71 (52.5%) children endorsed a change in pain score representing a MCSD, ICSD, and PPAA, respectively, that was higher than the estimates we identified. For the FPS-R, 57 (34.8%), 39 (41.1%), and 46 (29.3%) children endorsed a change in pain score representing a MCSD, ICSD, and PPAA, respectively, that was higher than the estimates we identified. There were a small number of children who reported an increase (rather than decrease) in pain score, despite endorsing a clinically meaningful decrease in pain: for the VNRS, there were 5 (2.3%) children who did so when endorsing an MCSD or ICSD, and 6 (4.4%) children who did so when reporting PPAA; for the FPS-R, there was 1 (0.4%) child who did so when endorsing an MCSD, and 6 (3.8%) children who did so when reporting PPAA. There were children of both younger and older ages in this cohort that reported an increase in pain score.
Figure 3. Changes in pain score associated with clinically meaningful outcomes in children using the Verbal Numerical Rating Scale and the Faces Pain Scale – Revised.
The maximum possible decrease in pain score is 10. Negative values represent an increase in pain score even though the child reported a subjective improvement in pain. VNRS = Verbal Numerical Rating Scale. FPS-R = Faces Pain Scale – Revised. MCSD = Minimum clinically significant difference. ICSD = Ideal clinically significant difference. PPAA = Patient-perceived adequate analgesia.
DISCUSSION
We have identified raw change and percent reduction in pain scores associated with clinically meaningful outcomes in children with acute pain using the VNRS and FPS-R. These changes in pain score appear to be similar across most patient characteristics, although we observed higher raw changes in pain score associated with higher initial pain intensity. Although we have determined the estimates that best identify the minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient-perceived adequate analgesia (PPAA) for most patients, we observed a wide range of scores reported by children associated with each outcome.
The changes in pain score we identified allow researchers to design trials based on clinically meaningful outcomes using two of the most commonly used self-report measures of pain in children. The PPAA, in particular, may be preferable to the MCSD or ICSD, neither of which necessarily represents a patient’s desired goal when seeking treatment for their pain. Our findings demonstrate that the raw change and percent reduction in pain scores representing PPAA are not consistently the same as those representing either the MCSD or ICSD when using the VNRS or FPS-R. In particular, the percent reduction in pain score representing PPAA was greater than the MCSD and less than the ICSD when both pain scales were used. This highlights the importance of asking a child a question that specifically addresses their own perception of whether they experienced adequate analgesia, rather than assuming that they experienced adequate analgesia just because they reported a change in pain score that was associated with a subjective decrease in pain that was “a little less” or “much less”.
Researchers may prefer to choose the percent reduction instead of raw change in pain score as a desired effect size for trials, given the variability in the raw change in pain score across different categories of initial pain intensity. The change in pain score required to experience a meaningful decrease in pain has been shown to differ based on a patient’s initial pain intensity: a higher initial pain intensity usually requires a greater decrease in pain to achieve a meaningful improvement.5,14,15 We observed a similar finding in our study, with the raw change scores required to achieve a MCSD, ICSD, or PPAA increasing with increasing initial pain intensity. However, the percent reductions in pain score associated with MCSD, ICSD, and PPAA appear to be more consistent and stable across the categories of moderate and severe pain intensity for both the VNRS and FPS-R. This would suggest that using a percent reduction in pain score might be a more generalizable estimate for effect size when studying the treatment of pain in children presenting with moderate to severe initial pain intensity.
We did not find any significant differences based on patient characteristics in our identified estimates of clinically meaningful outcomes. The changes in pain score representing each outcome were similar between the subgroups based on patient characteristics, suggesting that the estimates determined for MCSD, ICSD, and PPAA are generalizable across most populations. There were some variations noted in subgroups based on race/ethnicity and primary language, but these differences were not consistently observed in both pain scales, nor were they consistently present in both raw change and percent reductions in pain score within each subgroup or between each clinically meaningful outcome. The relatively smaller number of individuals available for analyses in some of these subgroups may have resulted in larger variability in these estimates and the observed differences in estimates identified.
The PPAA has not been previously described, but the MCSD and ICSD for the VNRS and FPS-R have been previously reported in similar populations of children with acute pain presenting to the ED. For the VNRS, Bailey et al. studied 202 children between the ages of 8 to 17 years, and identified an MCSD of 1/10 and an ICSD of 2.5/10.25 These estimates are lower than those identified in this current study. The difference may be due to differing analysis methods, with Bailey et al. using a distribution-based method to identify the median score associated with MCSD and ICSD, rather than the ROC-based methodology that we used. A ROC-based methodology may be preferable, as it allows one to select an estimate with optimal test characteristics, rather than being committed to whatever test characteristics are associated with a measure of central tendency. For the FPS-R, we previously studied 314 children between the ages of 4 to 17 years, and identified a raw change and percent reduction in pain score of 2/10 and 25%, respectively, for MCSD and a raw change and percent reduction in pain score of 3/10 and 60%, respectively, for ICSD.2 We used the same ROC-based methodology in this prior study, the results of which are similar to those observed in this current study.
Although these changes in pain score associated with clinically meaningful outcomes are useful for research, they are not useful on an individual patient basis. We observed a wide range of changes in pain scores associated with each outcome (Figure 3). A small number of patients even reported an increase, rather than decrease, in pain score to represent a MCSD, ICSD, or PPAA. If we were to use any of the changes in pain score identified in our study as a goal for treating individual patients, as many as 30-60% of them could potentially be inadequately treated for their pain. Therefore, our findings suggest that these changes in pain score associated with MCSD, ICSD, and PPAA may be useful as population-based estimates for research, but should not be used to guide treatment decisions for individual patients. What a patient perceives to be clinically meaningful, and whether a patient desires additional analgesia, is multifactorial: it is more complex than a single number, and is influenced by each patient’s individual pain temperament or sensitivity, proclivity towards medications, and degree of aversion regarding adverse events. 16,26–30 Rather than providing additional analgesia based solely on whether a certain change in pain score was achieved, it may be more appropriate for clinicians to ask whether or not the child desires additional analgesia, while taking into consideration the child’s personal preferences and perceptions and the clinical context.
LIMITATIONS
Our study has several limitations. We enrolled a convenience sample rather than consecutive patients, although our sample included a diverse representation of painful conditions, analgesics administered, and distribution of pain intensities. Changes in pain scores were reported to a member of the study team and not recorded in a blinded fashion, so subjects could have been subtly influenced to respond in ways that were consistent with the study team member’s expectations. We only studied children with acute pain, and did not include children with chronic or recurrent pain states, such as sickle cell disease. Our findings may not be generalizable to these children due to differences in how they perceive and respond to pain. 31–33 We did not document the reason why a child did not receive an analgesic, and do not know if it was because the child declined an analgesic, the clinician chose not to administer an analgesic, or for some other reason.
CONCLUSIONS
We have determined changes in pain score associated with a minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient-perceived adequate analgesia. Patient-perceived adequate analgesia may be a preferable and more patient-centered outcome than a MCSD and ICSD, and a percent reduction is more stable than a raw change in pain score across different categories of pain intensity. These population-based estimates of clinically meaningful outcomes are generalizable across different subgroups based on patient characteristics, and may be useful when selecting a desired effect size when designing trials. However, these changes in pain score are not appropriate for making treatment decisions at the level of the individual patient.
Supplementary Material
Acknowledgements:
We would like to thank Vartan Pahalyants, Allison Hyland, Jeffrey Sung, and Caitlin Oldenkamp for their assistance with patient enrollment.
Financial Support: This study was supported by Columbia University’s CTSA grant No. UL1TR000040 from NCATS/NIH, and the German Federal Ministry for Education and Research (BMBF #01EK1501).
Footnotes
Presentations: This paper was presented at the Pediatric Academic Societies Meeting (May 2017, San Francisco, CA, USA).
Conflict of Interest: None of the authors have any relevant conflicts of interest to disclose that might be perceived as a conflict of interest, although the corresponding author would like to disclose that he receives financial compensation as a consultant and member of the Clinical Events Committee for Tusker Medical (an otolaryngology medical device company that only makes a tympanostomy tube placement device) and is on the Board of Directors of the Society for Pediatric Sedation (no financial compensation). The author would be willing to cite these as conflicts of interest if the editors feel that these might be perceived as such.
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